61 results about "Drug Impurity" patented technology

The invention belongs to the technical field of biological medicine, particularly relates to a novel echinocandin drug impurity compound, and further discloses a preparation method and application thereof. Compared with a micafungin medicine structure, the echinocandin medicine impurity compound has the advantages that a hydrophobic acyl side chain is additionally arranged, side chain active ester is dissolved in a solvent firstly, a basic catalyst is added, and then a proper amount of FR179642 compound is added for reaction. The high-purity echinocandin drug impurity provided by the invention can be applied to quality control of echinocandin drugs, and can be used as a reference substance for establishing an analysis method.

The invention discloses a correlated imaging impurity detection method and system for drug production, and relates to the technical field of drug impurity detection. The method comprises the following steps: loading a first binary mask matrix, projecting a target product area, controlling a single-pixel detector to detect, determining a first measurement value, and performing lightweight reconstruction to obtain a first preview; generating a second binary mask matrix and performing projection and detection reconstruction by pre-checking the first preview, and performing multi-round iteration until an Nth preview is determined; calling the first preview to the Nth preview from a temporary database of an online detection platform, executing multi-layer compressed sensing and reconstruction, and determining a reconstruction result; and aiming at a reconstruction result, matching in an impurity feature library, and determining an impurity verification result. The technical problems of low impurity detection efficiency and insufficient detection accuracy in the medicine production process in the prior art are solved, and the technical effect of efficient and accurate online detection of medicine impurities in the production link is achieved.

The application belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of an indolebufen impurity. The application provides a novel synthesis method of the indolebufen impurity, wherein the compound 8 is prepared through a multi-step reaction. The synthesis method has reasonable process design, simple operation process, low cost, high yield and low cost of raw materials. The application can provide an impurity control sample for the research of drug impurities, thereby promoting the research of drug impurities, improving the quality standard of indolebufen drugs, guaranteeing the medication safety of the public, and having a positive significance.

The utility model relates to the field of pharmacy, and discloses a medicine impurity treatment device with a self-cleaning function, which comprises a protection box, the front side of the protection box is fixedly connected with an exhaust fan, the inside of the protection box is fixedly connected with a dust suction port, the bottom of the dust suction port is fixedly connected with a guide pipe, and the bottom end of the guide pipe is fixedly connected with a partition plate. And a first shell is fixedly connected to the left side of the protection box, a sliding rod is fixedly connected to the inner top wall of the first shell, the sliding rod is sleeved with a first spring, and an inserting rod is fixedly connected to the bottom end of the first spring. According to the dust collection device, the exhaust fan is driven to suck dust into the material collection frame from the dust collection opening through the guide pipe, the first pull rod is pulled to drive the first baffle to move forwards, the connecting rod is driven to be straightened, and the inserting rod is driven to work under the limiting of the sliding rod, so that impurities and dust are collected, and the material collection frame is conveniently and rapidly disassembled to be cleaned.

This invention relates to the field of pharmaceutical impurity preparation technology, and discloses a method for synthesizing apixaban genotoxic impurity I. The steps include: S1. performing an addition reaction of compound II in an alkaline system to generate compound III; S2. subjecting the product of S1 to elimination and isomerization reactions under heating, separating the reaction product to obtain apixaban genotoxic impurity I. The synthesis method of this invention has high safety, low raw material cost, and can achieve a one-pot reaction while ensuring yield and product purity (no product separation and purification is required between each reaction step; only one separation and purification is needed after obtaining the final product).

The invention relates to the technical field of medicine impurity purification, in particular to a separation and purification method of a high-purity urapidil impurity compound. Comprising the following steps: 1) performing vacuum concentration on urapidil mother liquor to obtain mother liquor concentrate M, adding dichloromethane, then adding 100-200-mesh silica gel, and performing vacuum concentration at 35-45 DEG C until the mother liquor concentrate M is dry; (2) weighing 200-300-mesh silica gel, adding dichloromethane, uniformly mixing, filling into a chromatographic column, and compacting for later use; (3) loading the vacuum concentrate in the step (1) into a chromatographic column, adding anhydrous sodium sulfate, and adding eluent for gradient elution; 4) collecting the eluent when the last eluent is used for elution, and performing reduced pressure concentration at 40-50 DEG C; after the concentration is finished, the urapidil impurity compound M1 can be obtained. According to the method for directly extracting and purifying the impurity compound from the mother liquor for preparing urapidil, the process is simpler, the purity of the purified impurity compound is 96-100%, and the accuracy and precision of the verification and detection method can be improved.

This application belongs to the field of drug detection. This application provides a method for detecting cyanamide impurities in drugs, including: successively adding a cyanamide reference substance or a test sample to an alkaline buffer solution and a dansyl chloride solution for derivatization reaction, and then using liquid chromatography tandem chromatography for detection, and calculating the content of cyanamide in the test sample by the standard curve method. The detection method of this application adjusts the derivatization reaction conditions by adding an alkaline buffer solution with a certain pH, making the derivatization product more stable; optimizing the liquid chromatography and mass spectrometry conditions, the resolution and peak shape of the derivatization product are good. The detection method of this application has excellent accuracy, sensitivity and stability, meets the various evaluation indexes of drug impurity detection, and can accurately determine the content of cyanamide impurities in drugs.

The invention belongs to the technical field of medicine synthesis, and relates to an intermediate for a bifunctional medicine as well as a preparation method and application thereof. The invention specifically discloses a compound shown as a formula (A), a plurality of preparation methods of the compound and application of the compound shown as the formula (A) in preparation of bifunctional drugs, the defects of high toxicity of raw materials, unstable intermediates, low yield and the like in an existing production process are overcome, the prepared bifunctional drugs are low in impurity content, the quality requirements of the drugs are met, and the application prospect is wide. And the preparation method provided by the invention can also realize industrial large-scale production. # imgabs0 #

This application discloses an analytical method for N-nitrosamine vortioxetine in vortioxetine hydrobromide tablets, belonging to the field of pharmaceutical impurity analysis. The method employs high-performance liquid chromatography (HPLC), with the following chromatographic conditions: a 4.6 mm × 250 mm column packed with octadecylsilane-bonded silica gel, with a particle size of 5 μm; mobile phase A is a 90:10 water-acetonitrile mixture containing 0.025%–0.035% trifluoroacetic acid (v / v); mobile phase B is acetonitrile; gradient elution; column temperature 38–42 °C; flow rate 0.9–1.1 ml / min; injection volume 50 μl; and detection wavelength 226 nm. This analytical method effectively eliminates excipient interference and exhibits excellent detection performance (specificity, sensitivity, linearity, precision, accuracy, and robustness), accurately detecting the content of N-nitrosamine vortioxetine in vortioxetine hydrobromide tablets, meeting quality control requirements.

The invention belongs to the technical field of biological medicine, particularly relates to a novel micafungin sodium drug impurity compound, and further discloses a preparation method and application thereof. The micafungin sodium drug impurity has a structure as shown in a formula (I), and the purity of the micafungin sodium drug impurity is greater than 95%. The high-purity impurity can serve as a reference substance for establishing an analysis method to be used for qualitative and quantitative analysis of impurities in micafungin sodium medicine, and technical support is provided for quality research of micafungin sodium.

The invention relates to the technical field of drug impurity synthesis, in particular to a preparation method of a lenalidomide impurity A. The preparation method comprises the following steps: (1) heating lenalidomide and a compound 1 in an alkali and solvent system, carrying out cyclization reaction, and carrying out column purification to obtain a compound 2, the compound 1 being 2-bromomethyl-3-nitrobenzoic acid methyl ester; and (2) reducing the compound 2 in an alcohol solvent and water system by using an inorganic metal reducing agent and a lewis acid system, and then concentrating, crystallizing, filtering and drying to obtain the lenalidomide impurity A. The invention provides a simple and efficient directional synthesis method of the lenalidomide impurity A. The method is low in cost, mild in condition, and suitable for industrial production. The lenalidomide impurity A is prepared by cyclizing lenalidomide and a compound 1 (lenalidomide intermediate, 2-bromomethyl-3-nitrobenzoic acid methyl ester) and then reducing, and the prepared lenalidomide impurity A is high in purity and can be used as an impurity reference substance for quality research of lenalidomide.

This invention discloses a method for preparing diosmin impurity compounds and their application, relating to the field of pharmaceutical impurity preparation technology. The preparation method includes the following steps: S1, preparation of compound IM-1: compound SM-1 and a methylating agent are heated under alkaline conditions to obtain compound IM-1; S2, preparation of compound formula 1: compound IM-1 is added to an alcohol solution, and an inorganic base is added under stirring. After the addition is complete, the mixture is kept warm and stirred, then cooled to 15-20°C, and dilute hydrochloric acid is added dropwise until the pH reaches 6.5-7. The mixture is concentrated to obtain the crude product of formula 1, and finally purified by thin-layer chromatography to obtain the pure product of formula I. This product can be used as a reference standard for the quality control of diosmin raw material, which helps to obtain a higher quality product.

The invention discloses a methimazole drug impurity as well as a preparation method and application thereof, and belongs to the technical field of organic synthesis. The preparation method of the methimazole drug impurity comprises the following steps: preparing a methimazole drug impurity intermediate 1, 2-bis (1-methyl-1H-imidazole-2-yl) disulfane by taking methimazole as a raw material, and then preparing a target compound methimazole drug impurity. The methimazole drug impurity with the purity up to 99.96% is prepared through two-step reaction, and a high-purity impurity standard substance is provided for a production process of an anti-thyroid drug methimazole and product quality control. The preparation method is short in process and fast and efficient in synthetic route.

The invention relates to the technical field of drug impurity detection, in particular to a method for detecting the content of dicyandiamide in a lamotrigine key intermediate. Respectively dissolving the test sample and the reference substance in a detection solvent to obtain a test sample solution and a reference substance solution; respectively separating the test solution and the reference solution by adopting a liquid chromatography technology, detecting by adopting a mass spectrometry detector, and calculating the content of dicyandiamide by adopting an external standard method according to a peak area; the liquid chromatography conditions are as follows: a C8 chromatographic column is adopted, and the flow rate is 0.45-0.55 ml / min; the column temperature is 30-40 DEG C; the mobile phase is A: 0.1% formic acid aqueous solution; b: acetonitrile; 8%-12% of A and 92%-88% of B are used for isocratic elution; the mass spectrometry conditions are as follows: in an ESI + positive ion mode, the taper hole voltage is 52V, the parent ion m / z is 85.2, the quantitative ion pair m / z is 85.2 / 68.4, the quantitative ion collision energy is 16V, the qualitative ion pair m / z is 85.2 / 43.5, and the qualitative ion collision energy is 14V. The methodology verifies that the method can be used for quantitatively detecting the content of dicyandiamide in the lamotrigine key intermediate.

The utility model discloses a recrystallization device for purifying medicine impurities, and relates to the technical field of medicine impurity removal. The filter screen frame is in contact with the upper side of the chassis; a plurality of extension blocks are distributed and fixed on the circumference of the bottom of the filter screen frame at equal angles, penetrate through the base plate and are exposed on the lower side of the base plate; the four fixing frames are fixedly arranged at the bottom of the base plate in a circumferential equiangular distribution mode. The four driving motors are fixedly arranged on one side of the fixing frame. The output end of the driving motor is arranged in the fixing frame after passing through the inner wall of one side of the fixing frame; the bidirectional screw rod is connected with the output end of the driving motor; the two-way lead screw is sleeved with two oppositely-arranged inserting frames through two oppositely-arranged threads on the two-way lead screw in a screwed connection mode, and the inserting ends of the inserting frames are inserted into the extending blocks. The two layers of filter screen rings are combined to form a filter screen frame, and activated carbon is placed in the filter screen frame; the active carbon is replaced by dismounting the net rack; therefore, the impurity removal efficiency is improved.

The application provides a echinocandin drug impurity, a preparation and purification method thereof and application. The echinocandin drug impurity has a structure shown in formula I: the echinocandin drug impurity is obtained by reacting micafungin sodium and a protonic acid aqueous solution, and high-purity echinocandin drug impurity is obtained after chromatographic purification. The echinocandin drug impurity obtained by the application can be used for quality control of echinocandin drugs as a control sample for establishing an analysis method.

The invention discloses a preparation method of nilotinib, which is characterized in that easily available industrial raw materials and common intermediates are adopted, and the nilotinib is prepared through optimized carbon-nitrogen coupling reaction. The preparation method has the advantages of easily available raw materials, simple process, mild conditions and few side reactions, can better control the generation and transmission of drug impurities, and improves the drug quality and safety. Compared with the prior art, the process can effectively reduce the production cost and reduce the environmental pollution, has industrial production prospects, and can promote the economic and technical development of the raw material medicine.

The application discloses a kind of drug production's associated imaging impurity detection method and system, it is related to drug impurity detection technical field.The method comprises the following steps: loading the first binary mask matrix, projecting target product area, controlling single-pixel detector to detect, determine the first measurement and light weight reconstruction into the first preview figure;Through pre-examination first preview figure, generate the second binary mask matrix and carry out projection and detection reconstruction, through multiple iterations until determine the Nth preview figure;From the temporary database of online detection platform, the first preview figure is retrieved until the Nth preview figure, multiple layer compressed sensing and reconstruction are executed, and the reconstruction result is determined;For reconstruction result, matching is carried out in impurity feature library, and impurity determination result is determined.The technical problem that the technical problem that the impurity detection efficiency is low and the detection accuracy is insufficient in the prior art in the production process of drug is solved, and the technical effect that the impurity of drug is efficiently and accurately detected in production link is achieved.

The invention relates to the technical field of drug impurity detection, in particular to a method for detecting the content of cyanamide in a lamotrigine key intermediate. Respectively dissolving the test sample and the reference substance in a detection solvent to obtain a test sample solution and a reference substance solution; respectively separating the test solution and the reference substance solution by adopting a liquid chromatography technology, detecting by adopting a mass spectrometry detector, and calculating the content of hydrazine by adopting an external standard method according to a peak area; the liquid chromatography conditions are as follows: a C18 chromatographic column is adopted, and the flow rate is 0.5-0.7 ml / min; the column temperature is 30-40 DEG C; the mobile phase is A: 0.1% formic acid aqueous solution; b: acetonitrile; 3%-7% of A and 97%-93% of B are used for isocratic elution; the mass spectrometry conditions are as follows: in an ESI-anion mode, the taper hole voltage is 52V, the parent ion m / z is 274.2, the quantitative ion pair m / z is 274.2 / 257.9, the quantitative ion collision energy is 31V, the qualitative ion pair m / z is 274.2 / 194.0, and the qualitative ion collision energy is 39V. The methodology verifies that the method can be used for quantitatively detecting the content of cyanamide in the lamotrigine key intermediate.

The invention relates to the technical field of drug impurity detection, in particular to a method for detecting the content of aminoguanidine in a lamotrigine key intermediate. Respectively dissolving the test sample and the reference substance in a detection solvent to obtain a test sample solution and a reference substance solution; respectively separating the test solution and the reference solution by adopting a liquid chromatography technology, detecting by adopting a mass spectrometry detector, and calculating the content of aminoguanidine by adopting an external standard method according to a peak area; the liquid chromatography conditions are as follows: a C8 chromatographic column is adopted, and the flow rate is 0.95-1.05 ml / min; the column temperature is 30-40 DEG C; the mobile phase is A: 0.1% formic acid aqueous solution; b: acetonitrile; gradient elution is carried out for 0.0 to 0.8 min, and 90 percent of A is obtained; when the time is 0.8-2.0 min, 90%-10% of A is added; in 2.0-4.0 min, 10% of A is taken; the mass spectrometry conditions are as follows: in an ESI + positive ion mode, the taper hole voltage is 38V, the parent ion m / z is 75.2, the quantitative ion pair m / z is 75.2 / 58.4, the quantitative ion collision energy is 11V, the qualitative ion pair m / z is 75.2 / 43.5, and the qualitative ion collision energy is 36V. The methodology verifies that the method can be used for quantitatively detecting the content of aminoguanidine in the lamotrigine key intermediate.

The invention belongs to the field of drug impurity detection and analysis, and particularly relates to a procaterol hydrochloride oral solution related substance detection method, which adopts high performance liquid chromatography, and the chromatographic conditions are as follows: a chromatographic column is an octadecyl silane bonded silica gel chromatographic column; the detection wavelength is 259 + / -5nm; the column temperature is 30-40 DEG C; the sample size is 10 to 100 [mu] l; the mobile phase A is a mixed solution composed of a phosphate buffer solution and methanol according to a volume ratio of (80-95): (5-20), and the pH value is 1.0-1.8; the mobile phase B is methanol; the flow velocity of the mobile phase is 0.3-1.5 ml / min; a gradient elution mode is adopted. The invention provides a novel method for detecting related substances in the procaterol hydrochloride oral solution, which not only can be used for detecting related impurities I, II and III of procaterol hydrochloride, but also can be used for detecting an auxiliary material degradation impurity 5-hydroxymethylfurfural in the procaterol hydrochloride oral solution at the same time, so that the impurity quality of a product is better controlled, and meanwhile, the detection efficiency is improved.

Provided are a high-purity echinocandin drug impurity, and a preparation method therefor and a use thereof. The structure of the echinocandin drug impurity is as shown in formula I, and the purity of the echinocandin drug impurity is greater than 90%.

The invention belongs to the technical field of drug synthesis, and particularly discloses a synthesis method of glycocholic acid dimer, which comprises the following steps: step 1, under alkaline condition, glycocholic acid and a condensing agent are condensed to obtain an active ester intermediate A; 2, carrying out a substitution reaction on the intermediate A and tert-butyl diphenyl chlorosilane under an alkaline condition to obtain an intermediate B; 3, under the action of a coupling reagent, the intermediate B and glycocholic acid are subjected to a coupling reaction, and an intermediate C is obtained; and 4, under the action of a deprotection agent, removing the tert-butyl diphenyl silyl group from the intermediate C to obtain the target product glycocholic acid dimer. According to the invention, a glycocholic acid dimer reference substance can be provided for research on impurities of glycocholic acid and related preparations thereof, so that research on drug impurities is promoted, and the method has positive significance for improving the quality standard of glycocholic acid drugs and guaranteeing the medication safety of residents.

The invention provides a preparation method and a filling and sealing method of a higenamine hydrochloride injection, due to the fact that higenamine hydrochloride is difficult to completely dissolve in water and can be degraded to generate impurities under the conditions of high temperature, oxygen, metal ions and the like, the higenamine hydrochloride is not easy to dissolve in water, and the higenamine hydrochloride is not easy to dissolve in water. The liquid preparation and potting method sequentially comprises a liquid preparation step, an ultrafiltration sterilization step and a potting step, liquid preparation is carried out under the nitrogen condition, the problem of solubility of higenamine hydrochloride can be effectively solved by adopting the liquid preparation mode, the generated medicine impurities are few, the potting effect is good, the reject ratio is low, and the production cost is low. The medicine quality of the higenamine hydrochloride injection is favorably guaranteed.

The invention discloses an analysis method for drug impurities, comprising the following steps: S1: preparing a sample solution for standby use; S2: adopting liquid chromatography, using a known impurity external standard method and an unknown impurity main component self-comparison method to calculate the impurity content, wherein mobile phase A is a salt solution, and mobile phase B is acetonitrile; the sample solution in step S1 comprises a first impurity reference substance stock solution, a second impurity reference substance stock solution, a test solution, a reference substance solution, a sensitivity stock solution and a sensitivity solution; the chromatographic column adopted in step S2 is Phenomenex Gemini C18, the detection wavelength is 332nm (VWD), the flow rate is 1.0ml / min, the column temperature is 35°C, the injection temperature is 4°C, and the injection volume is 10μl. The invention can effectively detect the content of relevant impurities in vometinib mesylate tablets, ensure that the produced products meet the quality standards, and ensure the safety of the products.

The utility model discloses a medicine impurity treatment device, which belongs to the technical field of medicine impurities and comprises a treatment box, a stirring box is fixedly connected to the top of the inside of the treatment box, a placing frame is fixedly connected to the inside of the treatment box and located at the bottom of the stirring box, and connecting grooves are formed in two sides of the top of the placing frame. A connecting frame is clamped in the connecting groove, and a dismounting groove is formed in the connecting frame, so that through the arrangement of the placing frame, the screening plate, a convex plate, a first spring, a cleaning plate, the connecting frame, a dismounting block, a push rod and a second spring, the screening effect on medicine impurities is achieved through the arrangement of the screening plate; and meanwhile, a cleaning plate is arranged to clean the screening plate, the situation that inconvenience exists in the using process due to the fact that screening and cleaning of the medicine impurities are inconvenient is avoided, the screening and cleaning effect on the medicine impurities is improved, and meanwhile the working efficiency of the medicine impurity treatment device is improved.

The utility model discloses a novel high-precision purification device for an apixaban intermediate, and relates to the technical field of medicine preparation. The device comprises a base, a purification tank is fixedly mounted on the base, a mounting cover is mounted at the top of the purification tank, a vertically-arranged rotating shaft is rotatably arranged at the middle end of the mounting cover, and a plurality of stirring pieces distributed at equal intervals are fixedly mounted at the end, located in the purification tank, of the rotating shaft. A horizontally-arranged cross rod is fixedly arranged at the top of the rotating shaft, a vertically-arranged first scraping plate is fixedly arranged at the end, away from the rotating shaft, of the cross rod, and an obliquely-arranged second scraping plate is fixedly arranged at the bottom of the first scraping plate; high-pressure water flow flushing of the fancy spraying head is combined with mechanical scraping of the first scraping plate and the second scraping plate, the double functions of spraying flushing and physical stripping are achieved, compared with a traditional single spraying mode, medicine impurities attached to the inner wall can be more thoroughly removed, and the cleaning efficiency is improved.

The invention relates to the technical field of drug impurity analysis, and discloses a method for detecting related substances of amphotericin B lipidosome. The amphotericin B lipidosome related substances comprise amphotericin B, an amphotericin impurity A, an amphotericin impurity B, an amphotericin impurity C, an amphotericin impurity D, an amphotericin impurity E, an amphotericin B glycosidic ligand and amphotericin B methyl ester, a mobile phase A of the liquid chromatography comprises a citric acid solution with the pH value of 4.7, acetonitrile and methanol, and a mobile phase B of the liquid chromatography comprises a mobile phase B of the liquid chromatography and a mobile phase B of the liquid chromatography; a mobile phase B of the liquid chromatography comprises a citric acid solution with the pH value of 3.9, acetonitrile and methanol. According to the method, the degree of separation of various amphotericin B liposome related substances is good, baseline separation is achieved, each impurity is attributed, a basis is provided for process research, tracking of the destination and trend of each impurity is facilitated, and stability research is further facilitated.

The utility model discloses an extraction device for chemical drug impurity detection. The extraction device comprises a drug impurity centrifugal extraction mechanism and a jacking mechanism arranged on the surfaces of a shell and a centrifugal extraction disc. The medicine impurity centrifugal extraction mechanism comprises a shell, a cover plate, a driving part and a centrifugal extraction disc, the cover plate is rotationally connected to the top of the shell through a damping rotating shaft, the driving part is installed on the inner wall of the shell, and the centrifugal extraction disc is installed on the surface of the driving part. The jacking mechanism comprises a transmission part and a jacking part. Solid particles or liquid drops in a mixture are separated according to the density and the size by means of centrifugal force generated by high-speed rotation, a test tube after centrifugation can be partially jacked out through the jacking mechanism, an inspector can conveniently take out the test tube, the test tube can be taken out without a tweezers tool after centrifugation is completed or when the test tube needs to be taken out by misplacement, and the operation is convenient. The head of the test tube can be exposed during opening and moved into the test tube during closing.

The invention discloses a preparation method of an atorvastatin calcium impurity J. The preparation method relates to the technical field of preparation of drug impurity standard substances, and specifically comprises the following steps: S1, carrying out heating reflux reaction on atorvastatin calcium 1 in a formula I under a strong acid condition to obtain a compound 2 and an atorvastatin calcium impurity H; and S2, hydrolyzing an atorvastatin calcium impurity J by using the compound 2 in the formula II under the action of second alkali. The method is reasonable in design and convenient to operate, and has the advantages of cheap and easily available raw materials, simple operation, short preparation period, easy purification, high yield and low production cost, and the prepared atorvastatin calcium impurity J is high in purity, has no obvious impurity points, meets the requirements of impurity reference substances, can be used as a standard substance of the atorvastatin calcium impurity J, and has wide application prospects. The method is applied to qualitative and quantitative research and detection of the atorvastatin calcium impurity J, and has certain significance on quality control of atorvastatin calcium bulk drugs and related preparations thereof.