Systems and methods for recycling solvents

Abstract

The system for separating the solvent includes a first mixing tank containing a waste solvent feed and a reactant feed, a first filter with a nanofiltration membrane, a distillation column or evaporator, a condenser or cooler, and a pervaporation membrane. The method for separating the solvent includes mixing the waste solvent with the reactants to cause precipitation or complexation to produce a mixture, filtering the mixture using the nanofiltration membrane to produce a permeate, distilling or evaporating the permeate to produce a concentrated solvent, condensing or cooling the concentrated solvent to below the boiling point of the solvent in the concentrated solvent, and filtering the concentrated solvent using pervaporation to produce a purified solvent. The system and method can separate and purify the solvent without producing pyrolysis products.

Description

Related Applications

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 325,463, filed March 30, 2022, the disclosure of which is incorporated by reference in its entirety herein. [Technical field]

[0002] The present disclosure relates to solvent recovery. The present disclosure further relates to filtration systems and methods for recovering solvents, such as those used in chromatography. [Background technology]

[0003] It is common for pharmaceutical companies to spend a lot of time and energy separating components of chemical mixtures into pure or purer forms. A groundbreaking 2016 study (1) estimated that purification processes such as distillation account for 10-15% of energy consumption in the United States. This is primarily due to manipulating chemicals through evaporation and subsequent cooling.

[0004] The pharmaceutical industry commonly uses chromatographic separation methods to purify drugs, which require large amounts of solvents. Storage and disposal of used solvents can be hazardous and costly. In order to reuse solvents, they must be purified to greater than 99% purity, as required by the U.S. Food and Drug Administration. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Sholl, D., and Lively, R., Seven chemical separations to change the world, 532 Nature 7600, 2016 Summary of the Invention [Problem to be solved by the invention]

[0006] There is a need in the art for sustainable separation methods to separate and reuse solvents used in chemical processes and separations. [Means for solving the problem]

[0007] SUMMARY OF THE DISCLOSURE Systems and methods are provided for recovering solvents, such as those used in chromatography.

[0008] A system for separating a solvent includes a first mixing tank with a waste solvent feed and a reactant feed, a first filter with a nanofiltration membrane configured to receive a stream from the first mixing tank, a distillation column or evaporator configured to receive a permeate from the first filter, a condenser or cooler configured to condense or cool the stream from the distillation column or evaporator, and a pervaporation membrane configured to receive the condensed or cooled stream from the condenser or cooler. The waste solvent feed may include a feed stream from a chromatographic separation system.

[0009] A method for separating a solvent includes mixing a waste solvent with a reactant to cause precipitation or complexation to produce a mixture, filtering the mixture using a nanofiltration membrane to produce a permeate, distilling or evaporating the permeate to produce a concentrated solvent, condensing or cooling the concentrated solvent to below the boiling point of the solvent in the concentrated solvent, and filtering the concentrated solvent using pervaporation to produce a purified solvent. The waste solvent may include a first solvent, a second solvent, and at least one contaminant. The reactant reacts with or complexes with the at least one contaminant. The waste solvent may include a chromatographic separation waste stream. The reactant may include a buffer. The reactant may include a base, where the reactant may optionally include sodium bicarbonate, magnesium chloride, iron(III) chloride, sodium hydroxide, trisaminomethane, polyethyleneimine, triethylamine, or a combination of any two or more thereof. The first solvent may comprise acetonitrile, ethanol, methanol, isopropanol, butanol, ethyl acetate, acetone, chloroform, diethyl ether, halothane, benzene, hexafluorobenzene, or a combination of any two or more thereof. The second solvent may comprise water or an organic solvent different from the first solvent. The purified solvent may comprise less than 500 ppm of pyrolysis products, where optionally the pyrolysis products comprise nitrosamines. [Brief description of the drawings]

[0010] [Figure 1] FIG. 1 is a schematic system diagram of a solvent recovery system according to one embodiment. [Diagram 2] FIG. 1 is a schematic flow diagram of a solvent recovery process according to one embodiment. [Diagram 3] FIG. 1 is a schematic system diagram of a solvent recovery system according to one embodiment. [Figure 4] 1 is a data graph of results obtained using a solvent recovery system according to one embodiment. [Diagram 5]FIG. 1 is a schematic system diagram of a solvent recovery system according to one embodiment. [Figure 6A-B] 1 is a graphical representation of data from Example 2. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] definition All scientific and technical terms used herein have meanings commonly used in the art unless otherwise specified. The definitions provided herein are intended to facilitate understanding of certain terms used frequently herein and are not intended to limit the scope of the present disclosure.

[0012] Unless otherwise specified, the terms "polymer" and "polymeric material" include, but are not limited to, organic homopolymers, copolymers (e.g., block, graft, random and alternating copolymers, etc.), terpolymers, and the like, as well as mixtures and modifications thereof. Furthermore, unless specifically limited, the term "polymer" is intended to include all possible geometric configurations of the material. These configurations include, but are not limited to, isotactic, syndiotactic, and atactic symmetries.

[0013] As used herein, the term "substantially" has the same meaning as "significantly" and can be understood to modify the following term with "at least about 90%, at least about 95%, or at least about 98%. The term "substantially free" of a particular compound means that the compositions of the present invention contain less than 1,000 parts per million (ppm) of the recited compound.

[0014] As used herein, the term "substantially not" has the same meaning as "not significantly" and can be understood to have the opposite meaning of "substantially," i.e., modifying the following term with "25% or less," "10% or less," "5% or less," or "2% or less."

[0015] As used herein, the term "about" is used in conjunction with numerical values ​​to include normal variations in measurement as would be expected by one of ordinary skill in the art, and is understood to have the same meaning as "approximately," and encompasses a typical range of error, such as ±5% of the stated value.

[0016] Terms such as "a," "an," and "the" are not intended to refer to only a single thing or thing, but are intended to include a general class of things of which one particular example may be used for illustration.

[0017] The terms "a" or "an" and "the" are used synonymously with the term "at least one." The phrases "at least one of" and "including at least one of," followed by a list, refer to any one of the items in that list, and any combination of two or more items in that list.

[0018] As used herein, the term "or" is generally used in its ordinary sense, including "and / or," unless otherwise clear from the context. The term "and / or" means one or all of the listed elements or a combination of any two or more of the listed elements.

[0019] The recitation of numerical ranges by endpoints includes all numbers subsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc.; or up to 10 includes 10, 9.4, 7.6, 5, 4.3, 2.9, 1.62, 0.3, etc.). When a range of values ​​is "up to" or "at least" a particular value, then that value is included in that range.

[0020] As used herein, "having," "including," "comprising," and the like are used in their open-ended sense, typically meaning "including, but not limited to." "Consisting essentially of," "consisting of," and the like are understood to be encompassed by "comprising," "including," and the like. As used herein, "consisting essentially of," when referring to a composition, article, method, and the like, means that the components of the composition, article, method, and the like are limited to the recited components and any other components that do not materially affect one or more basic and novel characteristics of the composition, article, method, and the like.

[0021] The words "preferred" and "preferably" refer to embodiments that may provide certain benefits, under particular circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the present disclosure, including the claims.

[0022] Any directions referred to herein, such as "up," "down," "left," "right," "upper," "lower," and other directions and orientations, are described herein with reference to the drawings for clarity and are not intended to limit the actual device or system or the uses of the device or system. The devices or systems described herein can be used in multiple directions and orientations.

[0023] FIELD OF THE DISCLOSURE The present disclosure relates to solvent recovery.The present disclosure relates to a filtration system and method for recovering solvents.The present disclosure further relates to a filtration system and method for recovering solvents used in chromatography.

[0024] The present disclosure provides a system and method for recycling solvents used during industrial-scale chromatography. According to an embodiment, the system and method can be used to recover (e.g., separate and purify) solvents used in chromatography to purify pharmaceutical ingredients. According to one embodiment, the system and method can be used to recover (e.g., separate and purify) solvents used in chromatography to purify a polypeptide solution. An example of a polypeptide solution is the solution remaining after insulin production and purification. According to one embodiment, the method of the present disclosure uses pervaporation. Pervaporation can be used to break azeotropes. The method may include additional steps to facilitate or improve the efficiency of pervaporation. For example, the method may include various precipitation, filtration, and / or distillation steps to remove contaminants and dilution solvents (e.g., water or another solvent).

[0025] Some organic solvents cannot be separated and purified simply by distillation due to the formation of azeotropes. Examples of organic solvents that form azeotropes with water include acetonitrile and ethanol. For acetonitrile, the azeotrope occurs at about 85% acetonitrile and 15% water. In order to recover and reuse the acetonitrile (e.g., after it has been used in a chromatographic separation), a concentration of 99% or more is desirable. It would be beneficial to provide a system and method that can be used to separate and purify a solvent regardless of its tendency to form azeotropes. It would be desirable to provide a system and method that does not result in the formation of thermal decomposition products such as nitrosamines or other additional contaminants in the liquid stream. It would be desirable to provide a system and method that can be used to separate and purify a solvent with less energy usage than conventional processes such as pressure swing distillation.

[0026] The term "waste solvent" is used herein to refer to a mixture that is a waste or by-product of another process (e.g., an industrial process such as an industrial separation process), and that includes at least a first solvent (the solvent of interest) and a second solvent. The waste solvent may include various other solvents and non-solvent impurities. According to an embodiment, the disclosed system and method can be used to process a waste solvent containing two or more solvents, separate at least one of the solvents (the solvent of interest), and concentrate the separated solvent. One of the solvents in the waste solvent may be an organic solvent. One of the solvents in the waste solvent may be water or another organic solvent. The solvent that is separated and concentrated may be an organic solvent, for example the first organic solvent. The solvent that is separated and concentrated may be the only organic solvent in the waste solvent. The concentration of the solvent of interest (e.g., organic solvent) in the waste solvent before separation is not particularly limited. In some exemplary embodiments, the concentration of the solvent of interest in the waste solvent is 5 vol% or more, 10 vol% or more, 15 vol% or more, 20 vol% or more, 30 vol% or more, 40 vol% or more, 50 vol% or more, or 75 vol% or more. The concentration of the solvent of interest in the waste solvent may be 99.5 vol% or less, 99 vol% or less, 98 vol% or less, 95 vol% or less, 90 vol% or less, 80 vol% or less, 70 vol% or less, 60 vol% or less, or 50 vol% or less. The waste solvent may include a second solvent (e.g., water or another organic solvent). The concentration of the second solvent in the waste solvent is not particularly limited. The second solvent (e.g., water or another organic solvent) may be included in the waste solvent at a concentration of, for example, 0.5 vol% to 95 vol%, 40 vol% to 90 vol%. According to one embodiment, the solvent of interest (e.g., an organic solvent) is separated from the second solvent (e.g., water or another organic solvent) and concentrated to a concentration of 90 vol.% or more, 95 vol.% or more, 96 vol.% or more, 97 vol.% or more, 98 vol.% or more, 99 vol.% or more, 99.5 vol.% or more, 99.8 vol.% or more, or 99.9 vol.% or more. The solvent of interest (e.g., an organic solvent) may be separated from the second solvent (e.g., water or another organic solvent) and concentrated to a concentration that exceeds the azeotropic concentration of the solvent of interest in a mixture of the solvent of interest and the second solvent.In one exemplary embodiment, the solvent of interest (e.g., an organic solvent) is present in the waste solvent at a concentration of 20 vol% to 60 vol% (e.g., about 30 vol%) and is separated from a second solvent (e.g., water or another organic solvent) using the systems and methods disclosed herein and concentrated to a concentration of 99 vol% or greater.

[0027] The concentration of non-solvent contaminants in the waste solvent can vary widely. The contaminants may be dissolved or suspended in the waste solvent. The contaminants may include inorganic compounds, organic compounds, biological compounds, and the like. If the waste solvent contains a large amount of contaminants (e.g., 10 wt% or more, or 5 wt% or more), the waste solvent may be first treated to remove most of the contaminants before separating and purifying the solvent of interest. In some embodiments, the waste solvent subjected to the method of the present disclosure contains contaminants at a concentration of 5 wt% or less, 2 wt% or less, 1 wt% or less, 0.5 wt% or less, 0.2 wt% or less, or 0.1 wt% or less. In some embodiments, the waste solvent is a waste solvent from a chromatographic separation. The contaminants may include the pharmaceutical ingredient, a reagent used to prepare the pharmaceutical ingredient, a by-product or degradation product of the pharmaceutical ingredient, or an impurity associated with the manufacture of the pharmaceutical ingredient.

[0028] The disclosed system and method can be used to separate many different types of solvents, such as organic solvents. The system and method can be particularly useful for separating solvents that form azeotropes with water or other solvents. Solvents that tend to form azeotropes are referred to herein as azeotrope-forming solvents. Examples of such solvents include acetonitrile, ethanol, methanol, isopropanol, butanol, ethyl acetate, acetone, chloroform, diethyl ether, halothane, benzene, and hexafluorobenzene. Other azeotrope-forming solvents exist. According to one embodiment, the solvent of interest is an azeotrope-forming solvent, and the system and method are configured for the separation and concentration of the azeotrope-forming solvent. The system and method are particularly useful for separating solvents from waste solvents that contain non-solvent components (e.g., contaminants), such as waste solvents used in the manufacture and / or purification of other chemicals, such as pharmaceutical ingredients. Acetonitrile is a solvent commonly used in HPLC chromatography, including at an industrial scale. According to one embodiment, the solvent of interest is acetonitrile, and the system and method are configured for the separation and concentration of acetonitrile. Acetonitrile may be present in an aqueous waste solvent stream.

[0029] The solvent of interest (e.g., organic solvent) and the second solvent (e.g., water or another organic solvent) may constitute a majority of the waste solvent. For example, the solvent of interest (e.g., organic solvent) and the second solvent (e.g., water or another organic solvent) may constitute more than 90 wt%, more than 95 wt%, more than 98 wt%, or more than 99 wt% of the waste solvent. The remaining portion of the waste solvent may include other solvents, buffers (e.g., acids, bases, or both), salts, relatively large residual molecules (e.g., pharmaceutical and biopharmaceutical components) and their degradation products, and other residual solids. In some embodiments, the waste solvent is a waste stream of a peptide manufacturing process (e.g., insulin manufacturing), and the relatively large residual molecules include residual peptides, truncated peptides, and peptide degradation products. The buffers and salts include those commonly used in the art in the manufacture of peptides or other pharmaceuticals.

[0030] The method of separating and concentrating waste solvent includes separating the non-solvent component from the solvent component and separating the solvent of interest from the second solvent and any optional additional solvents present in the waste solvent. Separating the non-solvent component from the solvent component may include one or more filtration steps, such as microfiltration, nanofiltration, ultrafiltration, or any combination thereof. Separating the non-solvent component from the solvent component may include nanofiltration, e.g., membrane filtration. Separating the non-solvent component from the solvent component may further include other steps, such as pH adjustment, buffering, complexing, performing other chemical reactions, and other (additional) filtration steps (e.g., microfiltration, nanofiltration, ultrafiltration, etc.), or any combination thereof. Separating the non-solvent component from the solvent component may include precipitating one or more of the non-solvent components and filtering out the precipitate.

[0031] According to one embodiment, the method includes a step of separating non-solvent components from solvent components before subjecting the waste solvent to high temperatures (e.g., in a distillation or pervaporation step). The waste solvent may be mixed with a buffer, another component, or a mixture of components. In some embodiments, the waste solvent is mixed with an acid or base. For example, if the waste solvent is acidic, it may be mixed with a base to raise or neutralize the pH. Raising or neutralizing the pH may be for compatibility with filtration membranes, such as nanofiltration membranes, that may degrade at low pH. Additionally, for example, by mixing a basic compound with the acidic waste solvent, the acidic molecules can be complexed with the basic compound, thus aiding in the separation of small acid molecules from the waste solvent by nanofiltration. The pH of the waste solvent can be raised by 1 to 3. Examples of basic compounds include inorganic bases, such as sodium bicarbonate; strong bases, such as sodium hydroxide; and organic bases, such as trisaminomethane, polyethyleneimine, and triethylamine. The waste solvent may also be mixed with one or more complexing agents, such as magnesium chloride or iron(III) chloride.

[0032] After mixing the waste solvent with a buffer, another component, or a mixture of components, the mixture is filtered to remove any solids, relatively large molecules, and complex compounds or ions (collectively referred to herein as contaminants). The contaminants may be dissolved or suspended in the waste solvent. In some embodiments, the filtration (e.g., the first filtration step) comprises microfiltration, nanofiltration, ultrafiltration, or any combination thereof. In some embodiments, the filtration (e.g., the first filtration step) comprises nanofiltration of the mixture. In some embodiments, the filtration comprises two or more filtration modalities. For example, the filtration may comprise a combination of microfiltration and nanofiltration. The filtration may comprise a combination of microfiltration, nanofiltration, and ultrafiltration. The filtration may comprise a combination of nanofiltration and ultrafiltration. In some embodiments, the mixture is filtered using nanofiltration. The nanofiltration may comprise the use of a nanofiltration membrane. The nanofiltration membrane may be selected based on the molecular weight of the contaminant. For example, the nanofiltration membrane may be selected to have a particular molecular weight cut-off, such as 100 Da, 200 Da, 500 Da, 750 Da, or 1000 Da. The nanofiltration membrane may be made of a polymeric material. An example of a suitable nanofiltration material is cellulose acetate. The permeate from nanofiltration contains a lower concentration of contaminants than the waste solvent, and the retentate contains a higher concentration of contaminants than the waste solvent.

[0033] According to one embodiment, most or substantially all of the non-solvent components are removed from the waste solvent before increasing the temperature of the waste solvent above ambient temperature (about 20° C.-25° C.) or above about 40° C. For example, most or substantially all of the non-solvent components are removed from the waste solvent before distillation or evaporation. In one exemplary embodiment, the waste solvent initially contains contaminants (other than the solvent of interest and a second solvent such as water) at a concentration of 0.01 wt % or more, 0.05 wt % or more, 0.1 wt % or more, 0.5 wt % or more, 1 wt % or more, 2 wt % or more, or 5 wt % or more. Although there is no particular upper limit on the amount of contaminants, in practice the waste solvent may contain up to 20 wt % or up to 10 wt % of contaminants. Contaminants may include both dissolved solids and suspended solids. After separating the non-solvent components from the waste solvent by nanofiltration, the remaining solvent stream may contain 1 wt% or less, 0.5 wt% or less, 0.2 wt% or less, 0.1 wt% or less, 0.05 wt% or less, or 0.01 wt% or less of non-solvent contaminants. After separating the non-solvent components from the waste solvent, the remaining solvent stream can consist of or consist essentially of the solvent of interest, the second solvent, and any subsequent solvents.

[0034] The step of separating the solvent of interest from the second solvent may comprise evaporation or distillation to remove at least a portion (e.g. a majority) of the second solvent. The method may comprise a second filtration step to further concentrate the solvent of interest. According to one embodiment, the evaporation step comprises feeding a liquid or gas-liquid mixture of two or more miscible components to an evaporator. The evaporator may be a single stage evaporator or a multi-stage evaporator. A heat source such as steam or hot oil may be used to partially evaporate the mixture. Compared to the feed waste solvent, the vapor formed is enriched in components with a lower boiling point and the bottom liquid is enriched in components with a higher boiling point. The vapor phase (enriched in components with a lower boiling point) and the liquid phase (enriched in components with a higher boiling point) may be removed separately from the evaporator. The vapor phase (enriched in components with a lower boiling point) may then be sent to a second filtration step (pervaporation) and the liquid phase (enriched in components with a higher boiling point) is removed from the process and either utilized for another purpose or treated as waste and disposed of.

[0035] In another embodiment, a distillation column is used instead of a single-stage evaporator to increase the purity of the separated components. In a typical distillation column, vapor flows upward through the column and liquid flows downward. At the bottom of the column, a liquid fraction called the "bottoms" is removed. The bottoms is enriched in components with higher boiling points compared to the feed waste solvent. A heat source (e.g., steam or oil) vaporizes the remaining liquid, thereby causing vapor to rise. At the top of the column, a condenser at least partially condenses the vapor exiting the column. The condensed liquid fraction is removed as a product "distillate." The distillate is enriched in components with lower boiling points compared to the feed. The remaining condensate is returned to the top of the column. The distillate may contain the solvent of interest in a concentration of 50 vol.% or more, 60 vol.% or more, 70 vol.% or more, or 80 vol.% or more, with the remainder consisting essentially of a second solvent (e.g., water or another organic solvent). The distillate may contain an azeotrope of the solvent of interest. The bottoms may contain the solvent of interest in concentrations of 50% or less, 40% or less, 30% or less, 20% or less, 10% or less, or 5% or less by volume, with the remainder consisting essentially of the second solvent (e.g., water or another organic solvent). The bottoms may contain the second solvent (e.g., water or another organic solvent) in concentrations of 50% or more, 60% or more, 70% or more, 80% or more, or 90% or more by volume. The ratio of liquid returned to the column to the liquid removed as distillate is known as the "reflux ratio" and is typically between 0 and 50, although there is no theoretical maximum limit. Heaters and condensers at either end of the column establish a temperature gradient along the column, ranging from the boiling point of the lowest boiling point component at the top to the boiling point of the highest boiling point component at the bottom. The column can be divided into stages by trays, such as bubble cap trays, sieve trays, or valve trays, or filled with packing material, such as perforated metal sheets or packing Raschig rings. The trays or packing material increase the surface area for contact between the vapor and liquid phases. This contact results in partial evaporation of the liquid and simultaneous condensation of the vapor throughout the column.Related to the temperature gradient, this causes the vapor to become enriched in lower boiling point components as it moves up the column, while the liquid becomes enriched in higher boiling point components as it moves down the column. Generally, the taller the column (more trays or higher packing height), the higher the purity of the exit stream.

[0036] In some embodiments, a liquid waste solvent containing both acetonitrile and water is fed to a distillation column. Acetonitrile, which boils at a lower temperature compared to water, is enriched in the vapor phase moving up the column. Water is enriched in the liquid phase moving down the column. The distillate product is primarily acetonitrile. However, distillation cannot concentrate the distillate further than the azeotrope, which is approximately 85 vol.% acetonitrile and 15 vol.% water. The bottoms product is primarily water, and may be greater than 90% or greater than 95% water and less than 10% or less than 5% acetonitrile.

[0037] After evaporation or distillation, the stream rich in the solvent of interest (hereinafter the term "enriched solvent" is used for brevity) can be further purified, while the stream rich in the removed solvent can be returned to the waste solvent stream or removed from the system. In one exemplary embodiment, the solvent of interest is acetonitrile and the acetonitrile rich stream is further purified, and the solvent to be removed is water and the water rich stream is returned to the waste solvent stream or removed from the system.

[0038] The concentrated solvent is then further purified in a second filtration step. The concentrated solvent (feed to the second filtration) may contain the solvent of interest at a concentration of 50 vol.% or more, 60 vol.% or more, 70 vol.% or more, or 80 vol.% or more, with the remainder consisting essentially of the second solvent (e.g., water or another organic solvent). The concentrated solvent (feed to the second filtration) may contain an azeotrope of the solvent of interest. The second filtration step may be selective for the solvent of interest or the second solvent. The second filtration step may include pervaporation, evaporation, or a combination thereof. In some embodiments, the second filtration step is a pervaporation step. Pervaporation is a separation process that typically uses selective membranes and a combination of permeation and evaporation. A pervaporation system may include a membrane with a feed side and a permeate side, and a vacuum is applied to the permeate side. The membrane may be selective for the solvent of interest. The permeate containing the solvent of interest can be recovered as a vapor downstream of the membrane and can be further condensed using a condenser. The pervaporation can be carried out in a pervaporation tower containing the membrane. The pervaporation membrane can be made of any suitable material. Examples of pervaporation membrane materials include thin films of polymers, such as poly(vinyl alcohol) or amorphous fluoropolymers, zeolites, silicates, hydrophilic functionalized hybrid silica, and combinations and composites of any two or more of these. For example, the pervaporation membrane can be made of a ceramic material, optionally coated with another material such as zeolite. The temperature and pressure used in the second filtration step can be selected to achieve the desired separation mode (e.g., pervaporation, evaporation, or a combination thereof). The temperature, pressure, and flow rate used in the second filtration step can also be selected to achieve the desired purity of the solvent of interest recovered. It may be desirable to operate the pervaporation using a combination of parameters that maintains the feed (concentrated solvent) below its boiling point. The combination of such parameters will depend on the particular combination of solvents.By way of example, when the enriched solvent is an acetonitrile-water mixture (e.g., an azeotrope of acetonitrile and water), the temperature and pressure of the pervaporation operation may be maintained below 76.4° C. and below 1 atm, or below 98° C. and below 2 atm, or below 112° C. and below 3 atm, or below 123° C. and below 4 atm, or below 131° C. and below 5 atm, etc. According to one embodiment, the enriched solvent is condensed and / or cooled after the distillation or evaporation step and before being introduced into the second filtration step (e.g., pervaporation). In some embodiments, the feed stream of the second filtration step (e.g., pervaporation) contains less than 0.1 wt. %, less than 0.01 wt. %, or no steam, based on the weight of the enriched solvent.

[0039] The concentrated solvent may be passed repeatedly through the pervaporation system until the purified solvent output stream has a solvent concentration of at least 90 vol%, at least 95 vol%, at least 96 vol%, at least 97 vol%, at least 98 vol%, at least 99 vol%, at least 99.5 vol%, at least 99.8 vol%, or at least 99.9 vol%. Depending on the selectivity of the pervaporation membrane, the purified solvent output stream can be the retentate or the permeate.

[0040] In some embodiments, the waste solvent is waste steam from a chromatography process. In some embodiments, the purified solvent exhaust stream is reused in the chromatography process.

[0041] In one exemplary embodiment, the method is used to separate a solvent of interest from a waste solvent, which is a mixture of the solvent of interest and a second solvent. The second solvent may be another organic solvent, a solvent mixture, or water. The mixture may also include other components (e.g., contaminants), such as buffers, pH adjusters, salts, residual peptides and peptide fragments, other residual solids, or any combination thereof. The mixture may include approximately 10-90 vol% of the solvent of interest. The mixture may be first mixed with one or more compounds that cause precipitation of one or more of the contaminants in the mixture. Precipitation-causing compounds include, for example, pH adjusters (e.g., acids and bases), salts, organic or inorganic compounds, etc., selected to react with one or more of the contaminants. In one embodiment, the mixture is buffered to a predetermined pH level with pH adjusters and any salts. The non-solvent components are then separated using a first filtration step. The first filtration step may be, for example, nanofiltration. The nanofilter may be selected based on the components that are desired to be removed. For example, the nanofilter may have a molecular weight cut-off of about 200 Da to 600 Da and may remove buffers, pH adjusters, salts, residual peptides and peptide fragments, and other residual solids from the solvent mixture. The filtered solvent mixture is then distilled, which removes at least a portion (e.g., most) of the second solvent. The distillate (distilled solvent mixture) may contain approximately 80 vol.% of the solvent of interest. The concentration of the solvent of interest can be adjusted by adjusting the distillation conditions (depending on the azeotrope). The distillate is further concentrated in a second filtration step. The second filtration step may be a nanofiltration step. The second filtration step may include pervaporation, evaporation, or a combination thereof. The temperature and pressure used in the second filtration step may be selected to achieve the desired separation mode (e.g., pervaporation, evaporation, or a combination thereof). The filter may be selected to be highly selective for the solvent of interest or the second solvent. In one exemplary embodiment, the second filter is a zeolite-containing filter that allows the second solvent to pass while retaining the solvent of interest.The temperature, pressure, and flow rate used in the second filtration step may further be selected to achieve a desired purity of the recovered solvent of interest. The solvent of interest may be recovered from the second filtration step with a purity of 90 vol.% or more, 95 vol.% or more, 96 vol.% or more, 97 vol.% or more, 98 vol.% or more, 99 vol.% or more, 99.5 vol.% or more, 99.8 vol.% or more, or 99.9 vol.% or more.

[0042] In one exemplary embodiment, the method is used to separate acetonitrile from a mixture of water and acetonitrile, which may contain other components such as buffers, pH adjusters, salts, residual peptides and peptide fragments, other residual solids, or a combination thereof. The mixture may contain approximately 20-50 vol.% acetonitrile. The mixture is first buffered to a predetermined pH value. The non-solvent components are then separated using nanofiltration. The nanofilter may be selected based on the components that are desired to be removed. For example, the nanofilter may have a molecular weight cut-off of approximately 200 Da to 600 Da and may remove the buffers, pH adjusters, salts, residual peptides and peptide fragments, and other residual solids from the solvent mixture. The filtered solvent mixture is then distilled, which removes at least a portion (e.g., most) of the water. The distillate (distilled solvent mixture) may contain approximately 80 vol.% acetonitrile. The concentration of acetonitrile can be adjusted by adjusting the distillation conditions (depending on the azeotrope). The distillate is further concentrated in a second filtration step. The second filtration step may include pervaporation, evaporation, or a combination thereof. The temperature and pressure used in the second filtration step may be selected to achieve the desired separation mode (e.g., pervaporation, evaporation, or a combination thereof). The filter may be selected to be highly selective for water or acetonitrile. In an exemplary embodiment, the second filter is a zeolite-containing filter that allows water to pass while retaining acetonitrile. The temperature, pressure, and flow rate used in the second filtration step may also be selected to achieve the desired purity of the recovered acetonitrile. Acetonitrile may be recovered from the second filtration step with a purity of 90 vol.% or more, 95 vol.% or more, 96 vol.% or more, 97 vol.% or more, 98 vol.% or more, 99 vol.% or more, 99.5 vol.% or more, 99.8 vol.% or more, or 99.9 vol.% or more.

[0043] An exemplary diagram of a system according to the present disclosure is shown in FIG. 1. The system 1 includes a feed line 11 to a first filter 10. The feed composition fed through the feed line 11 may be a waste solvent stream. The first filter 10 may be a nanofilter. The first filter 10 may include a separation membrane. The first filter 10 may be configured to remove components other than the solvent from the feed composition. Downstream of the first filter 10, the system 1 includes a distillation column 20. The filtered composition is conducted from the first filter 10 (e.g., from the permeate side of the first filter 10) to the distillation column 20 through a line 12. In the distillation column 20, the filtered composition is distilled to concentrate the solvent of interest. Thereafter, the concentrated solvent stream is conducted from the distillation column 20 to a second filter 30. The second filter 30 may be a nanofilter different from the first filter 10. The second filter 30 is configured to further concentrate the solvent to a desired final concentration. The second filter 30 may be configured to operate under conditions to concentrate the solvent of interest to a concentration higher than the azeotropic concentration of the solvent of interest and the second solvent. The second filter 30 has an outlet line 15 to discharge the purified concentrated solvent. The distillation column 20 may have an outlet line 14 to remove the second solvent from the system. The second filter 30 may also have an outlet line, such as a recycle line 16 to return a low concentration stream (e.g., retentate or permeate, depending on the configuration and arrangement of the filter) to the distillation column 20. In embodiments where the filter passes a high concentration of the solvent of interest and retains the second solvent, the retentate may be returned to the distillation column. In embodiments where the filter retains the solvent of interest, the permeate may be returned to the distillation column. The system 1 may further include additional components, such as storage tanks, mixing tanks, feed lines, bleed lines, outlets, valves, pumps, heaters, coolers, heat exchangers, etc.

[0044] In some embodiments, the method includes distillation of the permeate obtained from nanofiltration. A flow diagram of such a method is shown in FIG. 2. First, one or more reagents are mixed with waste solvent in a mixing tank. The mixture is then nanofiltered. The retentate can optionally be returned to the mixing tank or discarded as waste. The permeate obtained from nanofiltration is sent to a distillation column or evaporator. The bottoms of the distillation or evaporation may be discarded as waste. The distillate or evaporate may be cooled or condensed. The cooled or condensed mixture is then purified by pervaporation.

[0045] Another exemplary embodiment of system 2 is shown in FIG. 3. System 2 includes a buffer tank 50 that feeds a mixing tank 60 via a feed line 51 and a pump 52. The mixing tank 60 can be used to mix the waste solvent with a buffer, a pH adjuster, or other components that may facilitate separation of the non-solvent components from the solvent. The mixing tank 60 feeds a first filter 210 via a feed line 61 and a pump 62. The first filter 210 has a retentate side 211 and a permeate side 212. The retentate side 211 may feed a stream containing the non-solvent components to a first waste tank 81. The permeate side 212 feeds a solvent stream to a distillation column 220 via a line 214, a tank 215, and a pump 216. The line 214 may include a heat exchanger 217. The bottoms of the distillation column 220 containing the second solvent are fed to a second waste tank 82 through a waste line 221. The distillate (distilled solvent mixture) is fed to a second filter 230 (e.g., a pervaporation column) via line 224, tank 225, and pump 226. Line 224 may also include heat exchangers 227, 237. A vacuum pump 228 can be used to create a vacuum in the distillation column 220. Depending on the membrane in the second filter 230 selected, the solvent of interest may be present in either the retentate or the permeate of the second filter 230. In the illustrated exemplary embodiment, the purified solvent of interest is in the retentate line 231 and is directed to a recovery tank 240. The retentate line 231 may include a heat exchanger 238. The permeate may be directed to the second waste tank 82 via the permeate line 232. The permeate line 232 may further include a vacuum pump 234 and a heat exchanger 235. System 2 may further include additional components such as storage tanks, mixing tanks, supply lines, bleed lines, outlets, valves, pumps, heaters, coolers, heat exchangers, and the like.

[0046] Another exemplary embodiment of the system 3 is shown in FIG. 5. The system includes a tank 53 of waste solvent, which is pumped to a mixing tank 60. A buffer solution from the tank 50 is pumped to the mixing tank 60, which brings the waste solvent to the desired pH. Once at the desired pH, the waste solvent is pumped through a nanofilter 210 to remove non-solvent components. The permeate from the nanofilter 210 can be temporarily stored in a tank 70 before being transferred to a distillation column 220. The retentate can be circulated back to the mixing tank 60 or can be discarded. The distillation column 220 concentrates the solvent of interest. The distillate can be condensed in a condenser 222 and can optionally be collected in a tank 71. The concentrated second solvent (bottoms) can be collected in a waste tank 82. The distilled solvent of interest is repeatedly passed through a purity sensor S and a second filter 230 (pervaporation column) to be further concentrated. The pervaporation column is provided with a heating fluid from the tank 110. The second solvent can be drawn off under vacuum and collected in waste tank 83. Once the target purity is achieved for the solvent of interest, the system pumps the recovered solvent to tank 90. ​​The system may include a number of valves V, a pump P, and a condenser C. Additional valves, pumps, condensers, gauges, sensors, lines, storage tanks, controls, etc. may be included.

[0047] According to one embodiment, the first filter is selected based on the solvent and non-solvent desired to be removed from the solvent. The first filter may be selected to remove salts, acids, bases, complexed molecules, organic molecules other than the solvent, and other solids that may be present in the waste solvent.

[0048] In some embodiments, one or more non-solvent components of the waste solvent are reacted or complexed with another ion or molecule to facilitate separation from the solvent. Depending on the desired size of the resulting complex, molecule, or salt, the complexing agent or counterion may be monomeric, oligomeric, or polymeric. For example, trifluoroacetic acid (TFA), a small molecule commonly used as a pH adjuster in buffers (e.g., in peptide manufacturing processes), may be complexed or reacted with a base to facilitate removal. Exemplary bases that may be suitable for reaction with TFA include various amines, such as triethylamine, and its oligomeric and polymeric forms (e.g., polyethylamines).

[0049] According to one embodiment, the second filter is selected based on the solvent of interest and / or the second solvent. The second filter may be highly selective for the solvent of interest or the second solvent. For example, the second filter may be highly selective for organic solvents or water. The second filter may include a semi-permeable selective separation membrane. The second filter may be a separation membrane configured for pervaporation, evaporation, or a combination thereof. In one exemplary embodiment, the second filter is a separation membrane comprising an absorbent, adsorbent, or porous particles. Examples of suitable absorbents, adsorbents, and porous particles include zeolites, silica gels, ceramic particles, carbon nanotubes, and the like. The absorbent, adsorbent, or porous particles may be provided as a layer or embedded in the pores of the separation membrane. In one embodiment, the second filter includes a separation membrane with zeolite particles.

[0050] According to one embodiment, the system may include one or more instruments or sensors for monitoring the progress of the separation and purification throughout the method. For example, the system may include one or more sensors for detecting the concentration of the first solvent or the second solvent or both. Such sensors may be operatively connected to a control system and used to control various parameters of the operation of the equipment, such as temperature, pressure, residence time, etc. Examples of sensors that may be included in the system include capacitance, dielectric, and optical measurement systems. Capacitive and dielectric systems operate by measuring the dielectric constant of the mixture of liquids in the waste stream. Examples of these systems are available from Liebherr (Bühl, Switzerland). Optical measurement systems operate by measuring the light absorbed or scattered by the waste solvent. The attenuation of light passing through the solvent is typically measured at ultraviolet, infrared, or near infrared wavelengths and is a combination of attenuation due to all chemical species present in the light beam path. Examples of ultraviolet and infrared sensors are available from Pendotech (Princeton, NJ). The scattered light is used in Raman spectroscopy and contains information of all chemical species present in the light beam path. An example of a Raman detector is available from Wasatch Photonics, Inc. (Orlando, Fla.). In one embodiment, the system includes one or more sensors capable of measuring water content. In one embodiment, the system includes one or more sensors capable of measuring acetonitrile content. In one embodiment, the system includes one or more sensors capable of measuring water content during pervaporation. In one embodiment, the system includes a water sensor configured to measure water content downstream of the pervaporation membrane.

[0051] In one or more embodiments, the system may be described as including a controller. Such a controller may include one or more programmable processors including processing capabilities (e.g., a microcontroller or programmable logic circuitry), data storage (e.g., volatile or non-volatile memory or storage elements), input devices, and output devices. Program code or logic circuitry described herein may be applied to input data to perform the functions described herein to generate desired output information. The output information may be applied as input to one or more other devices or processes, as described herein or applied in known manner. The exact configuration of the controller is not limited, and essentially any device capable of providing suitable computing and control capabilities to perform the method may be used.

[0052] According to one embodiment, the process conditions during the separation and concentration steps are selected to prevent or minimize thermal decomposition products in the waste solvent and product streams (solvent of interest and low-concentration solvent streams). Thermal decomposition products can be compounds formed when one or more contaminants or solvents are exposed to high temperatures. The method can be used to separate and purify acetonitrile such that the resulting purified acetonitrile contains less than 500 ppm, less than 200 ppm, less than 100 ppm, less than 50 ppm, less than 20 ppm, less than 10 ppm, or less than 5 ppm of thermal decomposition products. For example, the method can be used to separate and purify acetonitrile without forming nitrosamines. The method can be used to separate and purify acetonitrile such that the resulting purified acetonitrile contains less than 500 ppm, less than 200 ppm, less than 100 ppm, less than 50 ppm, less than 20 ppm, less than 10 ppm, or less than 5 ppm of nitrosamines. The resulting purified acetonitrile is free or substantially free of nitrosamines. Thus, it may be desirable to avoid very high temperatures (e.g., temperatures above 140° C.) and high temperature and pressure combinations (e.g., temperature and pressure combinations commonly used in pressure swing distillation). The method can be carried out without raising the temperature of the waste solvent to 120° C. or more, 100° C. or more, 90° C. or more, 80° C. or more, 70° C. or more, or 60° C. or more. The method can be carried out without raising the temperature of the solvent of interest to 120° C. or more, 100° C. or more, 90° C. or more, 80° C. or more, 70° C. or more, or 60° C. or more. The method can be carried out without exposing the waste solvent to a combination of a temperature of 100° C. or more and a pressure of 250 kPa or more, a temperature of 80° C. or more and a pressure of 80 kPa or more, a temperature of 70° C. or more and a pressure of 60 kPa or more, or a temperature of 65° C. or more and a pressure of 30 kPa or more. The method can be carried out without exposing the solvent of interest to a combination of a temperature of 100° C. or greater and a pressure of 250 kPa or greater, a temperature of 80° C. or greater and a pressure of 80 kPa or greater, a temperature of 70° C. or greater and a pressure of 60 kPa or greater, or a temperature of 65° C. or greater and a pressure of 30 kPa or greater.

[0053] According to one embodiment, the separation and concentration method is carried out without adding another solvent to the mixture to act as an entrainer. For example, the method can be carried out without adding benzene to the waste solvent or the solvent of interest.

[0054] Embodiment A list of example embodiments is provided below.

[0055] In embodiment 1, a first mixing tank having a waste solvent feed and a reactant feed; a first filter having a nanofiltration membrane configured to receive flow from the first mixing tank; a distillation column or evaporator configured to receive the permeate from the first filter; a condenser or cooler configured to condense or cool a stream from the distillation column or evaporator; a pervaporation membrane configured to receive the condensed or cooled stream from the condenser or cooler; The system includes:

[0056] Embodiment 2 is the system of embodiment 1, wherein the spent solvent feed comprises a feed stream from a chromatographic separation system.

[0057] Embodiment 3 is the system of embodiment 1 or 2, wherein the waste solvent feed comprises a pharmaceutical ingredient, a reagent used to prepare the pharmaceutical ingredient, a by-product or degradation product of the pharmaceutical ingredient, or an impurity associated with the manufacture of the pharmaceutical ingredient.

[0058] Embodiment 4 is the system of any one of embodiments 1 to 3, further comprising a microfiltration filter disposed between the first mixing tank and the first filter or between the first filter and the distillation column.

[0059] Embodiment 5 is the system of any one of embodiments 1-4, further comprising an ultrafiltration filter disposed between the first mixing tank and the first filter or between the first filter and the distillation column.

[0060] Embodiment 6 is the system of any one of embodiments 1-5, wherein the condenser or cooler is configured to receive distillate from the distillation column.

[0061] In embodiment 7, mixing the spent solvent with the reactants to cause precipitation or complexation to form a mixture; filtering the mixture using a nanofiltration membrane to produce a permeate; distilling or evaporating the permeate to produce a concentrated solvent; condensing or cooling the concentrated solvent to below the boiling point of the solvent in the concentrated solvent; filtering the concentrated solvent using pervaporation to produce a purified solvent. The method includes:

[0062] Embodiment 8 is the method of embodiment 7, wherein the waste solvent comprises a first solvent, a second solvent, and at least one contaminant.

[0063] Embodiment 9 is the method of embodiment 7 or 8, wherein the waste solvent comprises contaminants at a concentration of at least 0.01 wt %, at least 0.05 wt %, at least 0.1 wt %, at least 0.5 wt %, at least 1 wt %, at least 2 wt %, or at least 5 wt %.

[0064] Embodiment 10 is the method of any one of embodiments 7-9, wherein the waste solvent feed comprises a pharmaceutical ingredient, a reagent used to prepare the pharmaceutical ingredient, a by-product or degradation product of the pharmaceutical ingredient, or an impurity associated with the manufacture of the pharmaceutical ingredient.

[0065] Embodiment 11 is the method of any one of embodiments 8 to 10, wherein the reactant reacts with or complexes with the at least one contaminant.

[0066] Embodiment 12 is the method of any one of embodiments 7-11, wherein the waste solvent comprises chromatographic separation waste steam.

[0067] Embodiment 13 is the method of any one of embodiments 7-12, further comprising sending the waste solvent from a chromatographic separation system to a mixing tank for mixing the waste solvent with the reactants.

[0068] Embodiment 14 is the method of any one of embodiments 7 to 13, wherein the reaction comprises a buffer.

[0069] Embodiment 15 is the method of any one of embodiments 7-14, wherein the reactants comprise a base, and optionally sodium bicarbonate, magnesium chloride, iron(III) chloride, sodium hydroxide, trisaminomethane, polyethyleneimine, triethylamine, or a combination of any two or more thereof.

[0070] Embodiment 16 is the method of any one of embodiments 7-15, wherein the first solvent comprises acetonitrile, ethanol, methanol, isopropanol, butanol, ethyl acetate, acetone, chloroform, diethyl ether, halothane, benzene, hexafluorobenzene, or a combination of any two or more thereof.

[0071] Embodiment 17 is the method of any one of embodiments 7-16, wherein the first solvent is acetonitrile.

[0072] Embodiment 18 is the method of any one of embodiments 7-17, wherein the second solvent comprises water or an organic solvent different from the first solvent.

[0073] Embodiment 19 is the method of any one of embodiments 7-18, wherein the second solvent is water.

[0074] Embodiment 20 is the method of any one of embodiments 7-19, wherein the distillate comprises an azeotrope.

[0075] Embodiment 21 is the method of any one of embodiments 7-20, wherein the distillate comprises the first solvent in a concentration of 50 vol.% or more, 60 vol.% or more, 70 vol.% or more, or 80 vol.% or more.

[0076] Embodiment 22 is the method of any one of embodiments 7-21, wherein the distillate comprises 80 vol.% or more acetonitrile and 15 vol.% or less water, or about 85 vol.% acetonitrile and about 15 vol.% water.

[0077] Embodiment 23 is the method of any one of embodiments 7 to 22, wherein the permeate is free of non-solvent contaminants.

[0078] Embodiment 24 is the method of any one of embodiments 7-23, wherein after nanofiltration and before distillation, the waste solvent has a concentration of contaminants of 1 wt % or less, 0.5 wt % or less, 0.2 wt % or less, 0.1 wt % or less, 0.05 wt % or less, or 0.01 wt % or less.

[0079] Embodiment 25 is the method of any one of embodiments 7 to 24, further comprising microfiltration prior to said distillation.

[0080] Embodiment 26 is the method of any one of embodiments 7 to 25, further comprising ultrafiltration prior to said distillation.

[0081] Embodiment 27 is the method of any one of embodiments 7 to 26, wherein the method does not include a step of increasing the temperature of the waste solvent to 120°C or more, 100°C or more, 90°C or more, 80°C or more, 70°C or more, or 60°C or more.

[0082] Embodiment 28 is the method of any one of embodiments 7 to 27, wherein the method does not include exposing the waste solvent to a combination of a temperature of 100° C. or more and a pressure of 250 kPa or more, a temperature of 80° C. or more and a pressure of 80 kPa or more, a temperature of 70° C. or more and a pressure of 60 kPa or more, or a temperature of 65° C. or more and a pressure of 30 kPa or more.

[0083] Embodiment 29 is the method of any one of embodiments 7 to 28, wherein the method does not include increasing the temperature of the first solvent to 120° C. or more, 100° C. or more, 90° C. or more, 80° C. or more, 70° C. or more, or 60° C. or more.

[0084] Embodiment 30 is the method of any one of embodiments 7 to 29, wherein the method does not include exposing the first solvent to a combination of a temperature of 100° C. or more and a pressure of 250 kPa or more, a temperature of 80° C. or more and a pressure of 80 kPa or more, a temperature of 70° C. or more and a pressure of 60 kPa or more, or a temperature of 65° C. or more and a pressure of 30 kPa or more.

[0085] Embodiment 31 is the method of any one of embodiments 7 to 30, wherein the molecular weight cut-off of the nanofiltration membrane is 100 Da to 1000 Da.

[0086] Embodiment 32 is the method of any one of embodiments 7-31, wherein the purified solvent comprises less than 500 ppm, less than 200 ppm, less than 100 ppm, less than 50 ppm, less than 20 ppm, less than 10 ppm, or less than 5 ppm of pyrolysis products.

[0087] Embodiment 33 is the method of any one of embodiments 7-32, wherein the purified solvent contains less than 500 ppm, less than 200 ppm, less than 100 ppm, less than 50 ppm, less than 20 ppm, less than 10 ppm, or less than 5 ppm nitrosamines.

[0088] Embodiment 34 is the method of any one of embodiments 7 to 33, wherein the purity of the purified solvent is 90 vol.% or more, 95 vol.% or more, 96 vol.% or more, 97 vol.% or more, 98 vol.% or more, 99 vol.% or more, 99.5 vol.% or more, 99.8 vol.% or more, or 99.9 vol.% or more.

[0089] Embodiment 35 is the system of any one of embodiments 1 to 6, further comprising a control device and one or more sensors operably coupled to the control device, the one or more sensors being capable of detecting moisture content, solvent content, or both.

[0090] Embodiment 36 is the system of embodiment 35, wherein the one or more sensors include a water sensor configured to measure the water content downstream of the pervaporation membrane. EXAMPLES

[0091] Example 1 A laboratory-scale system like that in Figure 3 was constructed and tested using a mixture of acetonitrile (30.37 vol%) and water containing peptides with chain lengths of C20-C50, and TFA buffer (pH 2-3). The pH of the mixture was adjusted by adding 0.83 M sodium bicarbonate until the final mixture pH was 5.35. After pH adjustment, the concentration of acetonitrile was 23.48 vol%. Following pH adjustment, the dissolved solids of the mixture were removed using tangential flow filtration using an organic solvent nanofiltration cassette with a molecular weight cutoff of 300-500 Da (available from Evonik Industries AG, Essen, Germany). The feed spacer of the cassette was 31 mils thick, providing a total filtration area of ​​0.315 m 2 After multiple passes of the mixture through a filtration cassette, the dissolved solids content of the permeate was determined gravimetrically, indicating 75% removal compared to the feed mixture.

[0092] After removal of the solids, 1000 mL of the permeate mixture was subjected to simple distillation using a rotary evaporator. The feed to the evaporator was set at 50° C. and the condenser was set at a pressure of 200 mm Hg and a temperature of −5° C. Using this procedure, a 185 mL sample of condensate with a water content of 25.2% was produced. The condensate mixture was filtered to remove 0.013 m 2 The pervaporation was carried out using a 1000-milliliter pervaporation column (Media and Process Technology, Pittsburgh, PA) at a temperature of 80° C. and a feed rate of 8 mL / min. The vapor side of the pervaporation system was held under vacuum and attached to a condenser to collect water vapor. The water content of the retentate mixture was measured periodically using Karl Fischer titration and is shown in Figure 4.

[0093] It was observed that HPLC waste solvents contained water and other contaminants. Standard distillation methods could not effectively purify and purify the waste solvents for reuse. It was concluded that a combination of buffering, nanofiltration, evaporation, and pervaporation was the best method to successfully purify and purify HPLC waste solvents for reuse.

[0094] Example 2 The experiment of Example 1 was repeated using only the pervaporation components of the equipment shown in Figure 3. In this example, a mixture containing 300 mL of acetonitrile and 15 vol% water was pervaporated as outlined in Example 1. The feed flux to the pervaporator was 30-50 mL / min and the pressure on the retentate was held at 10 psi. The results of the pervaporation experiment are shown in Figures 6A and 6B. It was again observed that pervaporation was able to remove the water to a level low enough for reuse.

[0095] All references and publications cited herein are expressly incorporated by reference in their entirety into this disclosure, except where they directly contradict this disclosure. Although specific embodiments are illustrated and described herein, those skilled in the art will understand that the specific embodiments illustrated and described may be substituted with various alternative and / or equivalent implementations without departing from the scope of the present disclosure. It is not intended that the disclosure be unduly limited by the exemplary embodiments and examples described herein, which examples and embodiments are presented merely as examples, and the scope of the present disclosure is intended to be limited only by the claims.

Claims

1. a first mixing tank containing a waste solvent feed and a reactant feed; a first filter including a nanofiltration membrane configured to receive flow from the first mixing tank; a distillation column or evaporator configured to receive the permeate from the first filter; a condenser or cooler configured to condense or cool the stream from the distillation column or evaporator; a pervaporation membrane configured to receive the condensed or cooled stream from the condenser or cooler; A system including:

2. The system of claim 1 , wherein the waste solvent feed comprises a feed stream from a chromatographic separation system.

3. A precision filtration filter disposed between the first mixing tank and the first filter or between the first filter and the distillation column; an ultrafiltration filter disposed between the first mixing tank and the first filter or between the first filter and the distillation column; or both The system of claim 1 or 2, further comprising:

4. 3. The system of claim 1 or 2, wherein the condenser or cooler is configured to receive distillate from the distillation column.

5. mixing the spent solvent with the reactants to cause precipitation or complexation to form a mixture; filtering the mixture using a nanofiltration membrane to produce a permeate; distilling or evaporating the permeate to produce a concentrated solvent; condensing or cooling the concentrated solvent to below the boiling point of the solvent in the concentrated solvent; filtering the concentrated solvent using pervaporation to produce a purified solvent; A method comprising:

6. The method of claim 5 , wherein the waste solvent comprises a first solvent, a second solvent, and at least one contaminant.

7. The method of claim 6 , wherein the reactant reacts with or complexes with the at least one contaminant.

8. 8. The method of claim 5, wherein the waste solvent comprises chromatographic separation waste steam.

9. 8. The method of claim 5, further comprising the step of sending the waste solvent from a chromatographic separation system to a mixing tank for mixing the waste solvent with the reactants.

10. 8. The method of claim 5, wherein the reaction comprises a buffer.

11. 8. The method of any one of claims 5 to 7, wherein the reactants comprise a base, optionally sodium bicarbonate, magnesium chloride, iron (III) chloride, sodium hydroxide, trisaminomethane, polyethyleneimine, triethylamine, or a combination of any two or more thereof.

12. The method of claim 5, wherein the first solvent comprises acetonitrile, ethanol, methanol, isopropanol, butanol, ethyl acetate, acetone, chloroform, diethyl ether, halothane, benzene, hexafluorobenzene, or a combination of any two or more thereof.

13. The method of claim 5, wherein the second solvent comprises water or an organic solvent different from the first solvent.

14. 8. The method of any one of claims 5 to 7, wherein the permeate is free of non-solvent contaminants.

15. The method of any one of claims 5 to 7, wherein the distillate comprises an azeotropic mixture.

16. 8. The method of any one of claims 5 to 7, wherein after nanofiltration and before distillation, the waste solvent has a concentration of contaminants of 1 wt% or less.

17. 8. The method of any one of claims 5 to 7, further comprising microfiltration or ultrafiltration or both prior to said distillation.

18. 8. The method of any one of claims 5 to 7, wherein the method does not include a step of increasing the temperature of the waste solvent above 100°C.

19. The method according to any one of claims 5 to 7, wherein the molecular weight cutoff of the nanofiltration membrane is 100 Da to 1000 Da.

20. 8. The method of any one of claims 5 to 7, wherein the purified solvent comprises less than 500 ppm, less than 200 ppm, less than 100 ppm, less than 50 ppm, less than 20 ppm, less than 10 ppm, or less than 5 ppm of pyrolysis products, optionally comprising nitrosamines.

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