25 results about "Drug Impurity" patented technology

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.

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 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.

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 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 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 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 detection method and application of ezetimibe intermediate related substances, and belongs to the technical field of drug impurity detection. The method specifically comprises the following steps: dissolving a test article YZ1 by using acetonitrile-water as a solvent to obtain a test article solution; acetonitrile-water is used as a solvent to dissolve the standard substance YZ1 and the impurity standard substance YZ1-1, and a system applicability solution is obtained; an octadecyl silane bonded silica gel column is used as a chromatographic column, acetonitrile-water is used as a mobile phase, and the content of the related substances in the test solution is detected by adopting high performance liquid chromatography. According to the technical scheme provided by the invention, the impurities in the ezetimibe intermediate can be well separated from one another, and the content of the impurities in the ezetimibe intermediate can be accurately calculated. The method has the beneficial effects of accurate qualification, convenience, reliability and good repeatability.

The invention discloses a method for detecting N-nitroso bisoprolol impurities in bisoprolol amlodipine tablets, and belongs to the field of drug impurity detection. The method comprises the following steps: preparing a reference substance solution and a test sample aqueous solution (ultrasonic dispersion and constant volume centrifugation), and then detecting by adopting HPLC-MS / MS: a chromatographic column is a C18 column (the particle size is 2-3 microns, the inner diameter is 2.1-4.6 mm, and the length is 100-250 mm), a mobile phase contains 0.1-0.5% of formic acid, 5-20 mM of an ammonium acetate aqueous solution and methanol / acetonitrile, and gradient elution is carried out; the mass spectrum is in an ESI positive ion mode, MRM scanning is carried out, and characteristic ion pairs (parent ions 372 + / -1amu, daughter ions 145 + / -1amu and the like) are monitored. The method is simple and convenient in pretreatment, environment-friendly in solvent, high in sensitivity and good in durability, trace impurities can be accurately detected, and reliable support is provided for quality control of bisoprolol amlodipine tablets.

The invention relates to a carbetocin injection isomer detection method, and belongs to the technical field of polypeptide drug impurity analysis. The carbetocin injection isomer detection method comprises the following steps: detecting Ile position isomer impurities in 8-site Leu in a carbetocin raw material by adopting a high performance liquid chromatography; the adopted chromatographic conditions are as follows: octadecyl silane bonded silica gel is taken as a filling agent, acetonitrile-0. 02 mol / L ammonium acetate-0.03 mol / L monopotassium phosphate is taken as a mobile phase A, methanol-acetonitrile is taken as a mobile phase B, and gradient elution is performed; the detection wavelength is 210 to 230 nm; the column temperature is 40-70 DEG C; the flow velocity is 0.5 to 1.2 mL / min; and the sample injection volume is 10-40 [mu] L. The carbetocin injection isomer detection method is high in accuracy and good in sensitivity, repeatability and precision meet requirements, position isomer impurities can be accurately detected, and the product quality can be better controlled.

Provided are a novel echinocandin drug impurity compound, a preparation method therefor, and the use thereof. Compared with the structure of drug micafungin, the echinocandin drug impurity compound has one more hydrophobic acyl side chain. The method comprises first dissolving a side chain active ester in a solvent, adding a basic catalyst, and then adding an appropriate amount of a FR179642 compound for reaction. The provided high-purity echinocandin drug impurity can be applied to quality control of the echinocandin drug as a reference standard for establishing analysis methods.

The present application relates to the field of drug impurity inspection, and specifically provides a ternary doped system, a method for inspecting special impurity I in naproxen raw drug and preparation, and application. The ternary doped system is doped with ketoprofen, naproxen and special impurity I. The method is based on host-guest doped room temperature phosphorescence technology, and an analysis platform for detecting trace special impurity I in naproxen raw drug with high sensitivity is constructed, with a detection limit as low as 0.05%, meeting the 0.1% inspection limit requirement specified in the pharmacopoeia. The technology can not only realize the limited inspection of the impurity in naproxen granules or tablets through spectral analysis and visual means, but also can be successfully applied to real-time monitoring of dynamic changes of impurities in the production process of different dosage forms. The present application has the advantages of strong specificity, high sensitivity, low reagent consumption and the like, meets the growing demand of the pharmaceutical industry for process analysis technology (PAT) in the impurity inspection process, and has good application value in the quality control of naproxen drugs.

The invention discloses a preparation method of a drug impurity 4-boron (10B) acid-phenylalanine butyl ester hydrochloride, and relates to the technical field of boron drug impurity synthesis. The 2, 4-boron (10B) acid-phenylalanine butyl ester hydrochloride (compound 6) is obtained by carrying out hydrolysis reaction on a compound 5 under the conditions of acid IV and a solvent IV, and the specific reaction formula is as follows: R1 is any one protecting group of Cbz, Boc, Pht and Trt. According to the invention, the technical problem that in the prior art, a synthesis method of an impurity compound 4-boron (10B) acid-phenylalanine butyl ester hydrochloride is lacked, so that a proper detection method and a judgment basis are lacked to be provided for production and medication safety of L-10BPA is solved; the invention provides the preparation method of the impurity 4-boron (10B) acid-phenylalanine butyl ester hydrochloride, which is few in synthetic route steps and low in reaction difficulty.