FOR THE CHARACTERIZATION OF A MIXTURE OF SOLUTES

Abstract

A method for characterizing a solution S0 comprising a plurality of solutes, which includes at least the steps of: S10) in an initial step with index j=1: S11) preparing a sample of solution S0; S12) determining a quantity XPh,1 in one of the phases of the sample; S20) in successive subsequent steps: S21) diluting the sample by adding organic solvent and / or aqueous solution; S22) determining the quantity XPh,j at equilibrium in one of the phases (Ph) of the sample; S30) determining the quantity XTot for the entire sample; S40) calculating a proportion (fi) and / or lipophilicity (Di) of the solutes (Si) by solving a system of equations: (EA) or (EO) Fig.7

Description

Title of the invention: METHOD WITHOUT PHASE SEPARATION FOR THE CHARACTERIZATION OF A MIXTURE OF SOLUTES Technical field of the invention

[0001] The invention relates to the field of characterization of solutions or more precisely, of mixtures of solutes.

[0002] More specifically, the invention relates to a method for non-targeted characterization of a solution comprising a plurality of solutes which is based on a sequence of partitions, or separations, of these solutes between two immiscible liquid phases, respectively aqueous and organic.

[0003] This method finds application in all fields where one may wish to characterize an aqueous or organic solution without having to determine its composition.

[0004] Thus, it can notably find application for: • characterize an agricultural or industrial effluent with a view to its subsequent management, in particular an effluent of complex composition including, for example, solutes resulting from biotic or abiotic degradation (chemical, radiolytic or other); • assess the quality of a natural or industrial product, particularly of a food nature (and, by the same token, the reliability of the processes implemented for its cultivation, collection or manufacture, conservation and distribution); • assess the quality of water such as water from a treatment plant (and, therefore, the reliability of the treatment process used), sea water or water from a watercourse, a body of water, natural or artificial, or a water table; or • assess the degree of purity of synthetic substances, whether marked or not, and characterize the quantity and properties of any impurities contained in these substances. State of the art

[0005] There are many methods for characterizing a solution.

[0006] Among these methods, we distinguish so-called direct or “targeted” methods and so-called “non-targeted” methods.

[0007] Targeted methods aim to detect the presence of known solutes in the solution and, generally, to determine their concentration or chemical form (phases, speciation). These methods typically include a prior step of separating the solutes, for example, by liquid chromatography.

[0008] Furthermore, non-targeted methods have been developed to detect the presence in a solution of as wide a range of solutes as possible, including solutes that are still unknown and, therefore, never studied. Examples of non-targeted methods include the one based on the use of liquid chromatography coupled with high-resolution mass spectroscopy (or LC-HRMS) and which has been implemented in particular by Mondeguer et al. (Spectra Analyse 2012, 284, 25-33) to establish a metabolomic-type profiling of the bioactive toxins of phytoplankton that accumulate in shellfish, and by Fischer et al. (Trends in Analytical Chemistry 2021, 136, 116188) to monitor the presence of pesticides in food.

[0009] Generally speaking, non-targeted methods reach a stage of development allowing them to benefit from validation or accreditation but generally remain difficult to implement and insufficient when it comes to characterizing solutions of particularly complex unknown composition.

[0010] When partitioning a mixture of solutes between two immiscible phases, the ratio of the total solute concentrations in each phase provides a weighted average of the solute partition coefficients (Zhifen 2014, Patent CN104102826). A single measurement on a chemical equilibrium is therefore of little applicative interest.

[0011] A method for non-targeted measurement of the concentration of solutes has been proposed by document FR2109802. According to this method, the measurement of a succession of different partition equilibria makes it possible to differentiate solutes of different lipophilicity contributing to the same measured quantity X. To carry out a sequence, a simple possibility is to carry out at each new equilibrium state, the separation of the two immiscible phases, then to mix the isolated phases with a new immiscible phase (free from the measured quantity).

[0012] However, this method is relatively difficult to implement, due to the need to carry out a large number of solution sharing operations and the kinetics of the latter.

[0013] There is therefore a need for methods for the non-targeted characterization of mixtures of solutes that are relatively easy and quick to implement. Statement of the invention

[0014] To meet the need indicated above, the invention proposes a method for characterizing a solution - called solution So in the following -, without phase separation, this method being simple to implement and applicable to any solution, aqueous or organic, of unknown composition, regardless of the complexity of this composition.

[0015] This method comprises at least the following steps:

[0016] S10) during an initial step of index j=l:

[0017] IF 1) a sample is constituted comprising at least one volume of the solution So;

[0018] S12) we measure an extensive and conservative quantity XPh>i in one of the phases pH of the sample, the phase can be the organic phase (O) or the aqueous phase (A);

[0019] S20) during each of the subsequent steps of index j, for j=2 to N:

[0020] S21) a volume of an organic solvent SOTg and / or a aqueous solution Saq;

[0021] S22) we determine the quantity XPhjj at equilibrium in one of the phases (Ph) of the sample;

[0022] V0,j representing a volume of an organic phase of the sample and VAjj a volume of an aqueous phase of the sample, during the index step j;

[0023] S30) the quantity XTot is determined for the entire sample;

[0024] S40) a proportion fi and / or a lipophilicity Di of at least one of the solutes is calculated (If) in the solution by solving a system of equations: XTOT . (Ea) or

[0025]

[0026] where i is an index corresponding to the solute considered, fi is a proportion of the solute considered i in the solution So, and for each value of the index j considered, the equation EA or Eo is chosen according to whether the quantity X was determined for the aqueous phase or the organic phase during step S10 or S20 corresponding to the value of j considered. Thus, the method of the invention comprises the following steps: - An initialization step S10 for an index value j=l, in which a sample is formed from the solution So studied, and the quantity X is determined for this initial sample. This sample can be a sample of the pure solution So, or possibly a sample of it, diluted with an organic solution and / or an aqueous solution. The aqueous solution and / or the organic solution with which the sample is diluted must not modify the value of the quantity X of the sample of pure solution which was integrated into the initial sample. - A sequence of steps S20 for j, j=2.. .N, of dilution / measurement. At each of these steps, the sample is diluted by adding a quantity (generally varying from one step to another) of organic solution and / or solution aqueous; then, the quantity X is determined again, noted XPhjj for one of the phases of the sample, representative of the sample when the sample is at equilibrium. - In parallel, the total value of the quantity X for the sample is determined in step S30.

[0027] Carrying out these different steps makes it possible to obtain a set of N values ​​of XPh,j / XTot associated respectively with N values ​​of VO,j / VA,j.

[0028] Due in particular to the conservation of the magnitude during the dilution operations, the magnitudes XPh,j / XTot and VO,j / VA,j are linked by the equation system E.

[0029] This system is a system comprising 2j-1 unknowns: the proportions fi of the different solutes, and their respective lipophilicities Di. It comprises N equations. Consequently, as soon as a sufficient number of values ​​(N>= 2j) are acquired, the solutions of this system of equations can be determined.

[0030] Naturally, the proportions fi of the different solutes are linked by the condition of conservation of matter: Sfi = 1.

[0031] Furthermore, preferably each step S20 is carried out in such a way that the ratio VO,k / VA,k of the sample obtained after addition and at equilibrium is different from each of the ratios VO,j / VA,j obtained in the respective index steps k, k=l,j-1 preceding.

[0032] Most of the time, in step S22 the quantity XPhjj is determined at equilibrium by waiting for the sample to reach equilibrium, then by measuring the value of the quantity X.

[0033] However, in certain embodiments, in particular to save time if the kinetics of reaching equilibrium are slow, in step S22 the quantity XPhjj at equilibrium is determined as a function of a plurality of measurements of the quantity X carried out before reaching the equilibrium state.

[0034] Any numerical method suitable for solving the system of equations established in step S40 may be adopted.

[0035] Solving this system of equations provides both the proportions fi of the different solutes, and their respective lipophilicities. Naturally, depending on the circumstances, certain values ​​of solute proportions and / or lipophilicities can be fixed in advance.

[0036] It is thus possible in certain embodiments to determine the proportion(s) fi, and / or the lipophilicity(ies) Di, of only a portion of the solutes present in the solution So.

[0037] The resolution of this system of equations can be carried out in particular by a conventional regression method such as the least squares method, and this, by means of software of the Excel (registered trademark) or OriginLab (registered trademark) type.

[0038] As the hydrophilic / lipophilic character of solutes is an intrinsic property of the solutes and represents relevant information on a certain number of their properties such as, for example, their solubility in a medium such as the environment and, therefore, their fate in this medium, their toxicity, their bioaccumulation, etc., the method makes it possible to obtain useful information on the solution So but without having to determine its exact composition or to identify the solutes that it comprises.

[0039] In the present document, the term 'solute' may designate, depending on the context (or rather, depending on the characterized solution), either a given chemical compound present in the solution, or a set of chemical compounds present in the solution and having similar lipophilicity values. In the latter case, the term 'solute' therefore corresponds to a fraction of compounds present in the solution and having similar lipophilicity values. A single lipophilicity value, considered as representative of this fraction of compounds, may be assigned to this fraction of compounds, considered as a solute, to allow the resolution of the system of equations in step S40.

[0040] The quantity X can be any quantity making it possible to target a property of interest presented by the solutes or certain solutes of the solution So provided that this quantity is extensive and conservative.

[0041] By "extensive" quantity, we mean a quantity whose sum of values ​​for two disjoint systems is equal to the value of the quantity for the union of the two systems, which means concretely, within the framework of the method of the invention, that, for a given composition phase, the quantity X is proportional to the volume of this phase.

[0042] By "conservative" quantity, we mean a quantity which remains constant for an isolated system not exchanging matter with the outside, which means concretely, within the framework of the process of the invention, that the quantity X is conserved at each operation of addition of organic solvent or aqueous solution and that thus, in the absence of any removal of matter, the sum of the values ​​of X in the aqueous and organic phases obtained after the dilution operations remains equal to the value of X in the solution So.

[0043] Thus, the quantity X can in particular be a quantity chosen from a quantity of matter (molar, mass or other), a concentration (if the quantity of matter is related to a unit of constant volume), an absorbance, a fluorescence, a radioactivity, an opacity, a quantity contained of total organic carbon (TOC), a quantity contained of total nitrogen, a chemical oxygen demand (COD), a biochemical oxygen demand (BOD), a quantity of suspended matter (MES), a quantity contained of a targeted isotope, such as carbon 14 or tritium 3-H, a quantity of ozone contained.

[0044] To increase the precision of the method, it is preferable that during steps S20, the dilution operations are carried out in such a way that the ratio Vo,i / Va,i, for the lipophilic compounds, covers a wide range of values, and in particular reaches a high value (for example 103); and likewise, and for the hydrophilic compounds, the ratio Vo,i / Va,i also covers a wide range of values, and in particular reaches a very low value (for example 103).

[0045] Thus in certain embodiments, a ratio Vo,i / VA,i of the sample obtained during a step jl is less than or equal to 103 and / or a ratio VO,j2 / VA,j2 of the sample obtained during a step j2 is less than or equal to 103.

[0046] In certain cases, in particular when the nature and number of solutes are little known, the method is implemented in step S40 assuming that the solution contains 3 solutes, respectively hydrophilic, amphipolar and lipophilic, of known lipophilicities D1, D2 and D3, such that log DI < 1 for the hydrophilic solute, -1 < log D2 < +1 for the amphipolar solute, and D3 > +1 for the lipophilic solute.

[0047] The So solution is preferably an aqueous solution, in which case the Sorg solution is typically a water-immiscible organic solvent, optionally pre-hydrated (i.e. pre-equilibrated by contact with water), while the Saq solution is an aqueous solution which preferably has an ionic strength and a pH close to those of the So solution and which may therefore comprise, for this purpose, a background salt of the KC1 or NaC104 type and / or a pH buffer in appropriate proportions in water, preferably distilled.

[0048] The water-immiscible organic solvent is, for example, a C8 to C12 alcohol (such as n-octanol, n-decanol or n-dodecanol), a C5 to C16 alkane (such as n-hexane, n-heptane or n-octane), cyclohexane, an aromatic hydrocarbon (such as benzene, toluene, ethylbenzene or xylene), chloroform, etc. Among these, preference is given to n-octanol.

[0049] Alternatively, the solution So may also be an organic solution, in which case the solution Saq is typically water, preferably distilled, while the solution SOTg may be the same organic solvent as that which the solution So comprises in the case where the organic solvent of the solution So is known, or, failing that, one of the organic solvents previously mentioned, possibly previously hydrated, preference being given, here too, to n-octanol.

[0050] The method proposed according to the present disclosure is applicable in particular to the case where in the solution So, the solutes are organic solutes.

[0051] In a particular embodiment, the solution So is a solution containing a single solute, pure or assumed to be pure; the method is implemented so as to measure the lipophilicity of the solute in step S40, either to determine it, or most often to verify that the solute is indeed in the pure state in the solution.

[0052] In the latter case, the lipophilicity of the solute is already known; it is therefore recalculated when implementing the method. If the lipophilicity value determined when implementing the method does not correspond to the (already known) lipophilicity of the solute, it is concluded that the solute is not in the pure state in the solution.

[0053] In a particular embodiment, in step S40, a single proportion is determined, representing a proportion of dissolved organic matter.

[0054] For this implementation method, it is possible in particular to choose as quantity X a quantity from among the quantities which characterize the quality of the water. These quantities can be TOC, CT, BOD, COD, 14C, 3H.

[0055] In this case, the method can advantageously be used to quantify fractions of unknown mixtures, with their proportions and / or their lipophilicity properties (log D), which advantageously makes it possible to deduce properties of the mixtures studied, for example in terms of absorption on materials, confinement during transport in geobarriers, etc.

[0056] Other characteristics and advantages of the invention will appear on reading the additional description which follows and which is given with reference to the appended Figs.

[0057] It goes without saying that this additional description is given only as an illustration of the subject of the invention and in no way constitutes a limitation of this subject. Brief description of the Figures

[0058] [Fig.l] schematically illustrates the results expected during a liquid-liquid characterization of a solution containing a single solute;

[0059] [Fig.2] schematically illustrates, for two different mixtures, the contents of constituents of these mixtures as a function of their lipophilicity;

[0060] [Fig.3] represents the curves of evolution of the ratio Xa / XTOt as a function of the ratio Vo / Vtot, for the two mixtures presented in [Fig.2];

[0061] [Fig.4] schematically presents comparative elements showing the effective correspondence between the measured data and the theoretical data used during the implementation of the method according to the present disclosure;

[0062] [Fig. 5] illustrates, schematically and by way of example, the results of experiments carried out and having made it possible to validate the method according to the present disclosure;

[0063] [Fig.6] illustrates, schematically and by way of example, the parameter values ​​determined during the experiments illustrated by [Fig.5]; and

[0064] [Fig.7] is a block diagram representing the main steps of the method according to the present disclosure. Detailed description of the invention Theoretical reminders

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[0086] The partition coefficient of a solute A reflects the distribution of this solute between two immiscible phases, respectively aqueous and organic, which are brought into contact with each other. It is typically defined by a concentration ratio, hereinafter denoted D(A), according to equation (4): 40=¾ (1) in which: [A]org is the molar concentration of solute A in the organic phase at equilibrium, and [A]aq is the molar concentration of solute A in the aqueous phase at equilibrium. For a solute A that occurs in solution in several species (such as a weak acid that dissociates into a base A and a proton), the partition coefficient D(A) is defined by equation (5): in which: [A;]org is the molar concentration of each species of solute A in the organic phase at equilibrium, [Ai]aq is the molar concentration of each species of solute A in the aqueous phase at equilibrium. It is also possible to define the partition coefficient by a ratio in numbers of moles, noted below D'(A), according to equation (6): (3) in which: n(A)org is the number of moles of solute A present in the organic phase at equilibrium, n(A)aq is the number of moles of solute A present in the aqueous phase at equilibrium, Vorg is the volume of the organic phase, and Vaq is the volume of the aqueous phase. For a solute A which occurs in solution in several species, equation (6) becomes equation (7): ? . . / 1 ​​ / 1; I D (A) = (4) in which: n(Ai)org is the number of moles of each species of solute A present in the phase organic in equilibrium, and

[0087] n(A;)aq is the number of moles of each species of solute A present in the aqueous phase at equilibrium.

[0088] It should be noted that the partition coefficients D and D' are dimensionless and are generally expressed in the form of their base ten logarithm, hereinafter denoted respectively logD and log D'.

[0089] The partitioning of a solute A in solution between two phases, respectively aqueous and organic, leads to the following balances (5a), (5b), (6a) and (6b):

[0090] Caq = Co x (5a)

[0091] (5b)

[0092] x (6a)

[0093] n„s = l,0 x (6b)

[0094] in which:

[0095] Co is the initial concentration of solute A (or the sum of the initial concentrations of its species) in the solution subjected to partition,

[0096] Caq is the concentration of solute A (or the sum of the concentrations of its species) in the aqueous phase resulting from the partition,

[0097] Corg is the concentration of solute A (or the sum of the concentrations of its species) in the organic phase resulting from the partition,

[0098] n0 is the number of moles of solute A (or the sum of the moles of its species) initially present in the solution subjected to partition,

[0099] naq is the number of moles of solute A (or the sum of the moles of its species) present in the aqueous phase resulting from the partition, and

[0100] nOTg is the number of moles of solute A (or the sum of the moles of its species) present in the organic phase resulting from the partition.

[0101] The above theoretical reminders are illustrated by Figs. 1 to 3.

[0102] [Fig.l] represents the results expected during a liquid-liquid characterization of a solution containing a single solute.

[0103] The characterization is done by diluting the initial sample, so as to vary the V0 / VA ratio. In the case, for example, of successive additions of (organic) solvent at the different stages S20, the V0 / VA ratio therefore increases progressively; the Xo / XToT ratio therefore decreases progressively.

[0104] In the case of an amphipolar compound No. 1 (curve Ci), the lipophilicity is 1 (DI = 1, i.e. log DI = 0). The extraction of the compound towards the organic phase increases with the volume of the organic phase, i.e. XA / XT0T decreases when V0 / VA increases. At the same time, the value of Dl' varies, following the dotted curve Cr. Dl' becomes equal to DI when V0 / VA = 1, or Dl' = Dl = 1.

[0105] For a second, more lipophilic compound No. 2 (curve C2), D2 = 10 (log D2 = +1), extraction begins at lower V0 / VA ratios. Thus, the curve XA / XT0T = f(V0 / VA) has the same shape for both compounds, but since log D2 = (Log D1 + 1), the curve for compound 2 is shifted by one logarithmic unit towards the low V0 / VA ratios. The same is true for the curve D' = f(V0 / VA), whose shape is constant but which shifts along the abscissa axis depending on the value of D.

[0106] Figs. 2 and 3 differ from the case of [Fig.l] in that they now concern Soi, S02 solutions containing multiple compounds. The lipophilicity distribution of these compounds is reported in [Fig.2].

[0107] [Fig.3] represents, in solid lines, the curves of evolution of the ratio XA / XT0T, as a function of the ratio Vo / VTOT, respectively for a first and a second solution Soi, S02, and for the first compound No. 1. [Fig.3] also represents, in dotted lines, the curves of evolution of D' as a function of the ratio Vo / VTot, also for the first and second solution Soi, S02, and for the first compound No. 1.

[0108] When a curve represents a solution containing several compounds, the curve corresponds to the sum of the contributions of each solute, each contribution having a shape similar to the curve in [Fig.l].

[0109] It can be noted in particular that the second solution S02 has a lipophilicity curve D close to that of compound No. 1 (log D = 0). In particular, it is impossible to differentiate this solution from the first compound using a single measurement of the quantity X when the ratio V0 / VA is equal to 1, because the two curves C02 and Ci intersect at V0 / VA = 1. Conversely, there is a slight difference between the respective values ​​of XA / XT0T of the second solution compared to the first compound for all other values ​​of V0 / VA.

[0110] In conclusion, it is therefore possible to differentiate the solutes of a mixture, by measuring the “overall” partitioning of the compounds, as a function of the ratio of the phase volumes V0 / VA.

[0111] An example of implementation of the methods according to the present disclosure will now be presented in relation to Figs. 4 and 7.

[0112] The method presented aims to calculate the proportions f; and and the lipophilicities Di of different solutes Si, i=l...M present in a solution So. S10) Constitution of the initial sample

[0113] The initial step (j=1) includes the following two steps:

[0114] IF 1) a sample is constituted by a predetermined volume of the solution So-

[0115] S12) the quantity XPh>i is determined in one of the phases of the sample, in measuring the value of this quantity once the sample has reached equilibrium.

[0116] The quantity X can be any quantity making it possible to target a property of interest presented by the solutes or some of the solutes of the solution So provided that this quantity is extensive on the one hand, and conservative on the other hand, that is to say that:

[0117] iïX,i: = iïX,.li:.

[0118] Thus, it may in particular involve: • a quantity of matter (molar, mass or other) or a concentration (reduced to a quantity of matter by multiplying by the volumes of the solution So or of the measured phases) such as total organic carbon (TOC), total nitrogen (according to the Kjeldahl method), chemical oxygen demand (COD), biochemical oxygen demand (BOD), suspended matter (SS), etc., • of an absorbance at a given wavelength, • fluorescence at a given excitation or emission wavelength, • radioactivity (such as the activity of 14C for example), • colloid content, or • opacity.

[0119] Most often, the quantity X is simply measured once the sample has reached equilibrium.

[0120] However, particularly if the kinetics of reaching equilibrium are slow, the quantity X can be extrapolated, and thus can be determined from measurements of the quantity X carried out once the sample has been constituted (by dilution) at iteration j, these measurements being carried out before the sample reaches equilibrium. In this case the value of the quantity at equilibrium can be determined by any appropriate predictive method, in particular any method tending to predict a limit value of a quantity which tends to stabilize at a finite value over time.

[0121] S20) Successive steps of dilution of the sample and determination of the magnitude X after dilution

[0122] Then, iteratively in a succession of steps S20, for j=2..N, the following steps are carried out:

[0123] S21) a volume of the organic solvent Sorg and / or a aqueous solution Saq, such that the ratio Vok / VAjk of the sample obtained after addition and at equilibrium is different from each of the ratios VOj / VAj obtained at the respective index steps k, k=l,jl preceding; and

[0124] S22) we determine the quantity (XA>j) at equilibrium in the aqueous phase of the sample.

[0125] Voj represents the volume of an organic phase of the sample and VAjj the volume of an aqueous phase of the sample, during each step of index j.

[0126] S30) Determination of the quantity XTot for the entire sample

[0127] During step S30, the total value of the quantity X, denoted XTot, is determined for the entire sample.

[0128] Step S30 can be carried out at any time during steps S10 and S20 (or between two of these steps), the XT0T value not varying during successive dilutions.

[0129] S40) Calculation of the proportions fi and / or the lipophilicity Di of the solutes Si present in the solution

[0130] Finally, in step S40, the proportions fi and the lipophilicities Di of the solutes Si present in the solution So are calculated by solving the system of equations: r X ÆXP / \ (E a ) OR \ ' HAS / / r ^.,1^ y. ID, \ (Eo) l atot 1' i [ 1+0'121 I \ J * A; /

[0131] where i is an index corresponding to one of the solutes, fi is a proportion of the solute i in the solution So., the equation EA or Eo being chosen for step j depending on whether the quantity X was chosen for step S20 for the index j considered.

[0132] In the above presentation, the method has been presented in the case where the quantity X is measured in the aqueous phase. However, the measurement of the quantity in step S12, and the exploitation of the results in step S40 can be carried out from the determination of the quantity X in the aqueous phase as in the organic phase.

[0133] Similarly, in the above presentation, the method has been presented in the case where at each step S20, organic solvent is added. However, at each step S20, organic solvent, and / or aqueous solution can be added. The only constraints are that the added product does not modify the total XT0T quantity of the sample. In addition, preferably the sample, after dilution, should have a Vo / VToi ratio that was not achieved in the previous steps.

[0134] Experimental confirmation of process performance

[0135] An experimental verification of the effectiveness of the method according to the present disclosure was carried out. The results obtained are summarized in Figs. 4 and 5.

[0136] For this verification, an aqueous mixture is prepared from 3 standard compounds of different lipophilicities, benzoic acid AB, theophylline Th and benzi-midazole Bz, which are characterized by their respective lipophilicities: Log D(AB) = -1.24; log D(Th) = -0.02; log D(Bz) = +1.34.

[0137] The quantity X determined is the quantity of matter, determined from the concentration, this being measured by UV-Visible spectroscopy.

[0138] In step S10 (which merges with step S30 in the present case), the concentrations in the initial (aqueous) solution S0 are determined, in step S10 before any dilution: CO(AB) = 3.05.10 5 mol.L *, CO(Bz) = 5.97.10 5 mol.L *, C0(T) = 4.5610 5 mol.L *.

[0139] Then in steps S20, the successive values ​​of the ratio XAjj / XT0T are determined in the form of ratios of the quantity of material remaining in the aqueous phase relative to the total quantity of material in the sample, at each step of index j, nAji / nT0T ([Fig.4]) (this illustration remaining valid for any other method of measuring an extensive and conservative quantity X).

[0140] Then in step S40, for each of the three compounds, the EA equations are established.

[0141] Firstly (and optionally), a preliminary calculation is carried out assuming that the solution contains a single fictitious dissolved compound X (M = 1). The lipophilicity D of the compound is then the only adjustable parameter. The modeled curve Cx corresponding to this first preliminary calculation is represented in [Fig.4] and the corresponding parameters in [Fig.5]. [Fig.4] presents the theoretical curve of the evolutions of the ratio XA / XT0T as a function of the ratio V0 / VA, for the 3 compounds AB, Th and Bz as well as for the fictitious dissolved compound X. [Fig.4] also presents the experimental values ​​Pj determined at the different stages S10 and S20, each experimental data being of the form (V0 / VA; XA / XT0T).

[0142] [Fig.4] shows a good relative agreement between the theoretical and adjusted log Di values, within an uncertainty range of ±0.3: this preliminary calculation makes it possible to verify the proper conduct of the experiment and the uncertainties intrinsic to the manipulations and not to the process in question.

[0143] Then, the system of equations EA is solved by effectively taking into account the presence of three compounds (AB, Th and Bz). We therefore determine the proportion of each compound (fi) and its lipophilicity (Di), from the XA / XT0T ratios. 5 parameters are adjusted simultaneously: fl, f3, Dl, D2, D3, the proportion f2 being fixed from the conservation of matter equation, i.e. f2 = (1 -fl - f3).

[0144] The results obtained are shown in [Fig.4]. A good relative agreement is obtained between the adjusted and theoretical Di values. The largest deviation obtained is 0.45 in the case of log D(theophylline). For the quantities also, a relative agreement is obtained with a deviation of at most 20%. These uncertainties can be reduced in different ways: - by increasing the number of points measured along the curve XA / XT0T = f(V o / VA), - by expanding the range of values ​​of the V0 / VA ratio used, (ideally from 103 to 10+3), and / or - by carrying out the measurement in two different ways, namely by adding solvent to the water (increasing V0 / VA) or by adding water to a solvent sample (decreasing V0 / VA) in order to improve the accuracy of the experimental input data. Evaluation of the robustness of the process

[0145] Further tests were conducted to evaluate the validity of the method proposed in the present disclosure. The results of these tests are illustrated in Figs. 6 and 7.

[0146] The robustness of the process was evaluated based on two parameters: the number of compounds mixed, and the number of measurements (of different V0 / VA ratios).

[0147] Figs. 6 and 7 represent the results obtained in the case of a solution containing 3 solutes SI, S2 and S3, having the following proportions fi and lipophilicity Di: fl = 52%, log DI = -2.91; f2 = 12%, log D2 = 0.23; f3 = 36%, log D3 = +2.13.

[0148] Following the “classical” interpretation model, we first assume that the 3 solutes form 3 fractions, respectively lipophilic, intermediate, and hydrophilic, that is to say that their lipophilicities are in the following ranges: for Dl, the range [-3; -1]; for D2, the range [-1; +1]; and for D3, the range [+1; +3], with respective proportions f1, f2, f3.

[0149] The method is executed by varying the number of measurements carried out in steps S10 and S20, as well as the range of values ​​covered by the V0 / VA ratio.

[0150] Three series of results are obtained ([Fig.6]): For case #1: 10 measurements are carried out, the V0 / VA ratio varies from 2.10-3 to 1; case #2: 10 measurements are carried out, the V0 / VA ratio varies from 10-2 to 10+2; case #3: 30 measurements are carried out, and it is considered at step S40 that the solution contains 5 different solutes.

[0151] For each of the series of results, Figs. 6 and 7 represent in a comparative manner the values ​​obtained in the case of the theoretical mixture and the results obtained on the basis of the measurements carried out.

[0152] For cases #1 and #2, the 6 variables calculated using the method (in step S40) are the proportions of the three solutes (or “fractions”) fl, f2, f3, and their respective lipophilicities Dl, D2, D3, i.e. 5 independent parameters, given the condition fl+f2+f3 = 1. The results obtained as shown in [Fig.7] are satisfactory, in particular for the lipophilic solute (D>1). However, a significant difference is observed for the hydrophilic solute (D < -1), whose extraction is low at V0 / VA of the order of 1. But these tests allow us to see that better precision can be achieved by widening the range of values ​​of the V0 / VA ratio: The process of case #1, carried out with 10 measurements but over a wider range of V0 / VA ratios going from 102 to 10+2 in case #2 leads to more precise results, in particular for the hydrophilic fraction.

[0153] Finally, for case #3, as indicated above, the method was executed assuming at step S40 that there is a higher adjusted number of solutes present, namely 5 solutes instead of 3. The model deviates slightly from the data measured for high VO / VA ratios (greater than 10+2); however, the results obtained by the method remain overall very close to the theoretical values. It should be noted that the estimated proportions f4 and f5 for the two solutes S4 and S5 (with respective lipophilicities log D4 = 1.5 and log D5 =2.5), worth 16 and 24% respectively, correspond in total to a value of 40% which is close to the theoretical value of the lipophilic compound (Itheor = 36%, log DTHeor = 2.13) and shows that the results obtained by the method for case #3 remain consistent, even if too large a number M of solutes has been taken into account. References cited

[0154] Mondeguer et al., Spectra Analyse 2012, 284, 25-33

[0155] Fischer et al., Trends in Analytical Chemistry 2021, 136, 116188

[0156] Dagnelie and Disdier, 2023. FR2109802

Claims

Claims

1. Method for characterizing a solution So comprising at least one solute, which comprises at least the following steps: S10) during an initial step of index j = 1: S11) a sample is constituted comprising at least one volume of the solution So; S12) an extensive and conservative quantity XPhji is determined in one of the phases of the sample, the phase possibly being the organic phase (0) or the aqueous phase (A); S20) during each of the subsequent steps of index j, for j = 2 to N: S21) a volume of an organic solvent Sorg and / or an aqueous solution Saq is added to the sample; S22) the quantity XPhjj is determined at equilibrium in one of the phases (Ph) of the sample; V0,j representing a volume of an organic phase of the sample and V Ajj a volume of an aqueous phase of the sample, during step of index j; S30) we determine the quantity XTot for the entire sample;S40) a proportion (fi) and / or a lipophilicity (Di) of at least one of the solutes (Si) in the solution is calculated by solving a system of equations: j_L_vEa)or L ^TOT 1' i 1 1+D 1 \ ' * .-1- / / [ ]£XP V r \ (Eo) Y — L^f ■ * V, L ^TOT J ! ]+D>. ] where i is an index corresponding to the solute considered, fi is a proportion of the solute considered i in the solution So, and for each value of the index j considered, the equation EA or Eo is chosen according to whether the quantity X was determined for the aqueous phase or the organic phase during step S10 or S20 corresponding to the value of j considered.;

2. The method of claim 1, wherein the quantity X is a quantity selected from an amount of matter, a concentration, an absorbance, a fluorescence, a radioactivity, an opacity, a contained amount of total organic carbon (TOC), a contained amount of total nitrogen, a chemical oxygen demand (COD), a biochemical oxygen demand (BOD), an amount of suspended matter (SS), a contained amount of a targeted isotope, such as carbon 14 or tritium 3-H,, ​​an amount of ozone contained.

3. Method according to claim 1 or 2, wherein a VOji / VAji ratio of the sample obtained during a step jl is less than or equal to 103 and / or a Voj2 / VAj2 ratio of the sample obtained during a step j2 is less than or equal to 10+3.

4. A method according to any one of claims 1 to 3, wherein in step S40, it is assumed that the solution contains 3 solutes (S1, S2, S3), respectively hydrophilic, amphipolar and lipophilic, of known lipophilicities D1, D2 and D3, such that log DI < 1 for the hydrophilic solute, -1 < log D2 < +1 for the amphipolar solute, and D3 > +1 for the lipophilic solute.

5. A method according to any one of claims 1 to 4, wherein the solution So is an aqueous solution.

6. A method according to claim 5, wherein the Sorg solution is a water-immiscible organic solvent and the Saq solution is water, preferably distilled, optionally comprising a background salt and / or a pH buffer.

7. A method according to claim 6, wherein the organic solvent is a C8-C12 alcohol; a C5-C16 alkane, for example n-hexane, n-heptane or n-octane; cyclohexane; an aromatic hydrocarbon, for example benzene, toluene, ethylbenzene or xylene; chloroform; or n-octanol.

8. A method according to any one of claims 1 to 4, wherein the solution So is an organic solution.

9. A method according to any one of claims 1 to 6, wherein the solutes are organic solutes.

10. Method according to any one of claims 1 to 9, in the case where the solution So is a solution containing a single solute, pure or assumed to be pure; the method is carried out so as to measure the lipophilicity of the solute in step S40, either to determine the latter, or to verify that the solute is indeed in the pure state in the solution.

11. A method according to any one of claims 1 to 9, wherein in step S40, a single proportion is determined, representing a proportion of dissolved organic matter.

12. Method according to any one of claims 1 to 11, in which in step S22, the quantity (XPhjj) at equilibrium is determined as a function of a plurality of measurements of the quantity X carried out before reaching a state of equilibrium.

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