81 results about "Genotoxic impurities" patented technology

The invention discloses a method for detecting a genotoxic impurity 6-[[3-(2-methoxyphenylamino)propyl]amino]-1,3-dimethyluracil in an urapidil hydrochloride raw material medicine. The method has good separation, strong specificity, high sensitivity and good accuracy, and can control the genotoxic impurity 6-[[3-(2-methoxyphenylamino)propyl]amino]-1,3-dimethyluracil in the urapidil hydrochloride raw material medicine, thereby ensuring the quality of a final product and the safety of medication.

The present invention relates to mirabegron substantially free from genotoxic impurities particularly nitrosamine impurities of Formula (I), (II), (III), (IV), (V) and processes for its preparation. In particular, the invention relates to processes for the preparation of high purity mirabegron free from nitrosamine impurities of Formula (I), (II), (III), (IV), (V) and other genotoxic and carcinogenic impurities below threshold concentration.

The invention discloses a method for detecting genotoxic impurities in vortioxetine hydrobromide orally disintegrating tablets. The method comprises the following steps: mixing phosphate buffer and methanol, wherein the volume ratio of the phosphate buffer to the methanol is 1-20:80-100, to obtain a solvent; grinding the vortioxetine hydrobromide orally disintegrating tablets, adding the mixture into the solvent for dissolution, filtering, and obtaining a test solution; then detecting the test solution by an HPLC method to obtain the content of the genotoxic impurities in the flutioxetine hydrobromide orally disintegrating tablets; the structural formula of the genotoxic impurities is shown in formula (I): The detection method of the invention has accurate and reliable results, is simple and convenient to operate, is rapid, has high stability, good repeatability and durability, can effectively break the difference between solubility and stability, has a recovery rate close to 100%, and has no significant degradation trend of nitrosamine impurities.

The invention relates to a method for detecting genotoxic impurities of rupatadine fumarate, which is characterized in that a phosphate buffer solution is matched with acetonitrile, a high performance liquid chromatography method is adopted, a chromatographic column is a silica gel bonded octadecylsilane column, a gradient program is adopted for elution, and the content of the rupatadine fumarate genotoxic impurities in the rupatadine fumarate genotoxic impurities in the rupatadine fumarate genotoxic impurities is detected. Effective separation between rupatadine fumarate and genotoxic impurities and between genotoxic impurities can be achieved, accurate quantitative analysis can be achieved, and the quality of drugs can be effectively controlled.

The invention belongs to the technical field of pharmaceutical analysis, and discloses a method for determining two potential genotoxic impurities in carbon [13C]-urea by gas chromatography. Comprising the following steps: (1) preparing a sample solution; (2) preparing a reference solution; (3) taking nitrogen as carrier gas, and detecting by adopting a medium-polarity or weak-polarity chromatographic column separation system; and (4) calculating by a peak area through an external standard method to obtain the accurate contents of methyl carbamate and ethyl carbamate in the carbon [13C]-urea. The method disclosed by the invention is simple to operate, good in specificity, linearity, precision and accuracy and high in sensitivity, and can realize accurate detection of residual potential genotoxic impurities, namely methyl carbamate and ethyl carbamate, in the carbon [13C]-urea.

The invention relates to the technical field of pharmaceutical analysis, and particularly discloses a high performance liquid chromatography-mass spectrometry tandem method (HPLC-MS / MS) for detecting a genotoxic impurity L-alanine isopropyl ester in an emtricitabine-propofol tenofovir tablet. By optimizing chromatographic column selection, a mobile phase gradient elution procedure and mass spectrometric detection parameters, the method realizes exclusive, sensitive and accurate detection of the L-isopropyl alanine. The methodological verification result shows that the detection limit is 1.00 ng / mL, the quantification limit is 2.00 ng / mL, the linear range is 2.00-100.00 ng / mL (the correlation coefficient r is equal to 0.9994), the recovery rate is stabilized between 92% and 98%, and the precision and repeatability are good. The detection method has the advantages of high sensitivity and strong selectivity, is suitable for quality control of emtricitabine propofol tenofovir tablets, meets the control requirements of ICH M7 guide on genotoxic impurities, and has good practicability and popularization value.

The invention discloses a voriconazole dry suspension as well as a preparation process, medical application and a detection method thereof. The voriconazole dry suspension is prepared from voriconazole and cane sugar, wherein the particle size D10 of the sucrose is 1-8 [mu] m, the particle size D50 of the sucrose is 9-40 [mu] m, and the particle size D90 of the sucrose is 30-120 [mu] m; the particle size D10 of the voriconazole dry suspension is 10 to 70 [mu] m, the particle size D50 of the voriconazole dry suspension is 50 to 300 [mu] m, and the particle size D90 of the voriconazole dry suspension is 150 to 500 [mu] m. The voriconazole dry suspension provided by the invention has excellent stability, is still low in genotoxic impurities after long-term storage, can be suitable for normal-temperature transportation, storage and use, reduces the transportation and storage cost, and improves the use convenience of patients.

The invention discloses a genotoxic impurity detection method, which can simultaneously detect genotoxic impurities NDMA, NDPA and dimethyl sulfate, adopts a gas chromatography-mass spectrometry (GC-MS) technology, dissolves a sample through a formic acid-containing anhydrous / ultra-dry organic solvent, and combines chromatography-mass spectrometry conditions to realize efficient and synchronous detection of the three impurities. The chromatographic conditions are simple, the mass spectrum detection limit is excellent, the impurity stability is remarkably improved by the method, and the recovery rate RSD value is 1t; the method is good in detection specificity and high in precision, so that the genotoxic impurities in the medicine are effectively controlled, the quality of the medicine is guaranteed, the safety of clinical medication is further guaranteed, and the method has remarkable technical advantages and industrial application value.

The invention relates to the technical field of drug analysis and detection, and particularly discloses a method for detecting genotoxic impurities in lamotrigine. According to the method for detecting the genotoxic impurities in the lamotrigine, a Venusil XBP C18 (L) (150mm * 4.6 mm, 5mu m) chromatographic column is adopted, a mixed solution of a monopotassium phosphate solution-triethylamine and a mixed solution of acetonitrile are used as a mobile phase, and the genotoxic impurities (impurities K) in the lamotrigine are accurately detected in a gradient elution mode through a high performance liquid chromatography method. The detection limit of the impurity K is 0.0013 mu g / mL, the quantification limit is 0.0025 mu g / mL, and the detection requirements of the guiding principle of ICH M7 are met. The method provided by the invention has the advantages of strong specificity, high sensitivity, good linear relationship, good precision and durability, and can be used as a basis for monitoring the quality of lamotrigine drugs.

The invention discloses a method for determining the content of seven genotoxic impurities in epichlorohydrin through gas chromatography-mass spectrometry, and belongs to the technical field of pharmaceutical analysis. According to the method, a quartz capillary chromatographic column taking polyethylene glycol as a stationary phase is adopted, split-flow sample injection is performed, and the genotoxic impurities in an epoxy chloropropane sample are detected by using a gas chromatography-mass spectrometry method; the genetic toxicity impurities are glycidyl, 1, 3-dichloro-2-propyl alcohol, 2, 3-dichloro-1-propyl alcohol, 3-chloro-1, 2-propylene glycol, 2-chloro-1, 3-propylene glycol, 2-chloro-2-propylene-1-alcohol, and 1, 2, 3-trichloropropane. The invention further discloses a preparation method of the compound. According to the present invention, the seven genotoxic impurities in the epoxy chloropropane can be rapidly, effectively, accurately and reliably separated and detected, and the genotoxic impurities can be controlled within the low detection range through the mass spectrometer, such that the quality of the epoxy chloropropane can be easily controlled, the product quality of the hexyl aminolevulinate hydrochloride can be easily improved, and the medication safety of the patient can be easily improved.

The invention provides an HPLC (High Performance Liquid Chromatography) detection method for sulfonate impurities in calcium dobesilate, and relates to the field of medicine detection. Comprising the following steps: a chromatographic column is an octadecyl silane bonded silica gel chromatographic column; mobile phases: taking an ammonium dihydrogen phosphate solution as a mobile phase A and methanol as a mobile phase B; the elution mode is as follows: gradient elution is carried out, the adjustment range of the mobile phase A is 80-60% v / v, and the adjustment range of the mobile phase B is 20-40% v / v. By adopting the HPLC detection method disclosed by the invention, the contents of three genotoxic impurities, namely methyl 2, 5-dihydroxybenzenesulfonate, ethyl 2, 5-dihydroxybenzenesulfonate and isopropyl 2, 5-dihydroxybenzenesulfonate, in the calcium dobesilate raw material medicine are effectively determined, the sensitivity is high, the quantitation limit is low, the quality of the calcium dobesilate raw material medicine is better controlled, and the medicine safety is better guaranteed. On the premise that the detection effect is guaranteed, the detection method is simple and easy to operate, the detection cost is effectively reduced, and an impurity control scheme which is more economical, stable and easy to popularize is achieved.

The invention discloses a method for detecting benzyl bromide analogue impurities in an alogliptin benzoate raw material medicine, and relates to the technical field of medicine analysis and detection. According to the method, one-time detection of the three benzyl bromide analogue impurities in the alogliptin benzoate raw material medicine can be achieved, the detection sensitivity can reach the ppm (1 / million) level, and control over potential genotoxic impurities in the medicine can be better and more accurately achieved.

The invention discloses a high performance liquid chromatography detection method for trace genotoxic impurities in chlorpheniramine maleate, and belongs to the technical field of pharmaceutical analysis. According to the method, a chromatographic column taking octadecyl bonded silica gel as a filling agent is adopted, an ammonia water solution is taken as a mobile phase A, acetonitrile is taken as a mobile phase B, gradient elution is carried out, and genotoxic impurities in a chlorpheniramine maleate sample are detected by utilizing a high performance liquid chromatography; and the genotoxic impurities are 2-aminopyridine-N-oxide, 2-bromopyridine-N-oxide and 2-aminopyridine. The invention further discloses a preparation method of the genotoxic impurities. The method disclosed by the invention can be used for simultaneously detecting three trace genotoxic impurities, is high in sensitivity, good in separation degree and low in product matrix interference, can be widely applied to a high performance liquid chromatography detection method for determining the trace genotoxic impurities in the chlorpheniramine maleate, fully meets the qualitative and quantitative analysis of the trace genotoxic impurities in the product, and has a wide application prospect. And the product quality is effectively controlled.

The invention discloses an analysis method for a genotoxic impurity (2S)-2-amino-3-ethoxysulfinyl-3-methylbutyric acid in a sulbactam sodium raw material. The analysis method has strong specificity and high sensitivity, and can be used for monitoring the target product of the synthesis method of the invention, and can also be used alone for detecting the genotoxic impurity (2S)-2-amino-3-ethoxysulfinyl-3-methylbutyric acid in the sulbactam sodium raw material, thereby ensuring the safety of the drug. The reaction raw materials of the synthesis method of the impurity are simple and easy to obtain, and the reaction is carried out in only one step, and the operation is simple.

The present invention provides a method for simultaneously detecting multiple genotoxic impurities in a drug, wherein the genotoxic impurities are selected from one or more of budesonide triene impurity 5 (IM-5) of structural formula I and budesonide triene impurity 6 (IM-6) of structural formula II: wherein the method is liquid chromatography, and the liquid chromatography comprises the following chromatographic conditions: chromatographic column: a liquid chromatography column with core-shell octylsilane as a stationary phase; detection wavelength: 238-242nm; mobile phase A: 0.1v / v% phosphoric acid solution; mobile phase B: acetonitrile. The method of the present invention has good separation; no interference; strong specificity; high sensitivity; good linear relationship, can realize effective control of impurities in budesonide triene, and further ensures the product quality of budesonide and the drug safety of patients.

The invention belongs to the technical field of medical analysis, and discloses a pyrrole acyl piperidylamine compound and a method for detecting genotoxic impurities of the pyrrole acyl piperidylamine compound. Specifically, the invention relates to analysis and limit determination of four genotoxic impurities in a pyrroloyl piperidylamine new drug (code name compound 1) for resisting drug-resistant bacterium infection. According to the method, a liquid chromatography-mass spectrometry technology is adopted, octadecyl bonded silica gel is used as a stationary phase, a mixed solution of methanol and an ammonium acetate acidic aqueous solution is used as a mobile phase, and triple quadrupole mass spectrometry is used as a detector for analysis and determination. The genotoxic impurities comprise halogenated alkanes, halogenated olefins, carbamates and azo oxides. The method has relatively good specificity and sensitivity, can be used for accurately and quantitatively determining the genotoxic impurities, and is simple and rapid to operate. The method provides a method basis for quality control of the compound 1, and has important application value for quality control and safety guarantee in a new drug research and development process.

This invention discloses a method for detecting genotoxic impurities in fosfomycin calcium. The method involves preparing a test solution and a reference solution using hydrochloric acid as a solvent, and then detecting the test solution and reference solution using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS / MS) to obtain the content of genotoxic impurities in fosfomycin calcium. The genotoxic impurities are: 1,2-epoxypropyl diethyl phosphate, (2-propenyl)-diethyl phosphate, allyl diethyl phosphate, and propyl diethyl phosphate. This invention develops an analytical method capable of simultaneously detecting four diethyl phosphonate genotoxic impurities in fosfomycin calcium. This method exhibits good specificity, injection precision, linear range, limit of quantitation, limit of detection, accuracy, repeatability, intermediate precision, and robustness. It can be used for the detection and monitoring of diethyl phosphonate impurities in fosfomycin calcium raw materials, ensuring product quality and improving the safety of clinical medication.

The invention belongs to the technical field of analysis and detection, and discloses a method for detecting impurities in a tadalafil bulk drug and / or a tadalafil intermediate. The method for detecting the impurities in the tadalafil bulk drug and / or the tadalafil intermediate comprises the following steps: taking the tadalafil bulk drug and / or the tadalafil intermediate to be detected, and preparing a sample solution; taking an impurity standard substance, and preparing a standard sample solution; and detecting the impurities in the sample solution by adopting an ultra-high performance liquid chromatography-mass spectrometry method. According to the detection method, two N-nitroso genotoxic impurities and ten other process impurities in tadalafil raw materials and / or tadalafil intermediates can be determined at the same time, the specificity is high, the sensitivity is high, results of multiple different types of impurities can be obtained at the same time in one-time determination, the analysis efficiency is effectively improved, and the method is suitable for popularization and application. Powerful guarantee is provided for analyzing generation factors influencing impurities, effectively controlling medicine quality and guaranteeing medicine use safety.

The invention discloses a method for detecting genotoxic impurities in dabigatran etexilate mesylate, and belongs to the technical field of pharmaceutical analysis. The detection method comprises the following steps: pretreatment of a sample: dissolving a dabigatran etexilate mesylate sample in an acid solution, extracting, then centrifuging the extract liquor, and taking supernate to respectively obtain to-be-detected solutions; the method comprises the following steps: pre-treating a genotoxic impurity standard substance according to a method which is the same as a method for pre-treating a dabigatran etexilate mesylate sample to obtain a standard solution; and measuring the standard solution and the to-be-measured solution by adopting a gas chromatograph-tandem mass spectrometer, and calculating according to the standard curve to obtain the content of each genotoxic impurity in the to-be-measured solution. According to the method, various genotoxic impurities and dabigatran etexilate mesylate are effectively separated through a liquid-liquid extraction method, the influence of dabigatran etexilate on genotoxic impurity analysis is reduced, interfering substances are reduced, and the method is high in accuracy and good in repeatability.

The invention relates to a method for determining three methanesulfonate genotoxic impurities in a prasefovir mesylate tablet by gas chromatography-mass spectrometry, and belongs to the technical field of pharmaceutical analysis. The invention relates to a method for determining three methanesulfonate genotoxic impurities in prasefovir mesylate tablets by gas chromatography-mass spectrometry. The method comprises the following steps: (1) preparing three single-standard stock solutions, a mixed standard solution and a mixed standard series solution; (2) preparing a test solution; (3) rapid qualitative screening; and (4) quantitative determination. The gas chromatography-mass spectrometry method (GC-MS method) has remarkable advantages in the aspects of operation simplicity, specificity, sensitivity, accuracy and the like, the method is simple in operation process, sample pretreatment is easy to implement, the detection time is greatly shortened, and the detection efficiency is improved.

The present application belongs to the technical field of pharmaceutical analysis, and particularly relates to a kind of analytical method for determining genetic toxic impurities in nilotinib composition.The present application has good specificity, simple operation, high sensitivity, low cost, and is suitable for frequent detection in mass production, etc., for determining impurity A in compositions such as nilotinib oral suspension, nilotinib dry suspension or nilotinib capsules.The method can effectively separate the nilotinib impurity A peak from its adjacent impurity peak, and solve the problem of easy damage of the chromatographic column during the determination of nilotinib impurity A.

The invention belongs to the technical field of drug analysis and detection, and particularly relates to a method for detecting potential genotoxic impurities in Vonoprasone fumarate and application. The invention discloses a high performance liquid chromatography method for detecting potential genotoxic impurities of Vonoprazan fumarate, which adopts a chromatographic column with octadecylsilane chemically bonded silica as a filler and adopts phosphate buffered solution-acetonitrile as a mobile phase for gradient elution. The potential genotoxic impurities in the Vonoprasone fumarate can be rapidly and effectively separated. The method has the advantages that the separation degree of each chromatographic peak and an adjacent impurity peak is good, the detection limit and the quantitation limit also meet the analysis requirements, the sensitivity and the accuracy are high, the detection of the potential genotoxic impurities of the Vonoprazan fumarate can be met, and the product quality is ensured.

The invention provides a mass spectrometric detection and analysis method for three genotoxic impurities in lamidetan hemisuccinate, which adopts a mass spectrometric detector, selects proper mobile phase, column temperature, flow velocity, chromatographic column and ion pair, performs quantitative analysis on the three impurities in lamidetan hemisuccinate, improves the detection means for quality control of a lamidetan hemisuccinate product, and improves the detection accuracy of the lamidetan hemisuccinate product. The method is convenient and feasible, has high accuracy, can effectively control the quality of lamidetan hemisuccinate, and improves the safety of drugs.

The invention provides a method for detecting impurities in budesonide, and belongs to the technical field of drug detection.The construction method comprises the steps that budesonide is used for preparing a test solution, then gas chromatography detection is conducted, and a chromatogram is obtained so as to detect the impurities in budesonide. As the micromolecular aldehyde substance is a genotoxic impurity of budesonide, the medication safety of budesonide can be better guaranteed by effectively detecting and controlling the micromolecular aldehyde substance, the invention constructs the method for detecting the impurity in budesonide, and the technical blank of detection of the micromolecular aldehyde substance in budesonide is well solved.

The invention discloses a quantitative analysis method of potential genotoxic impurities in cariprazine hydrochloride, which adopts a liquid chromatography-mass spectrometry method, takes a 20mM ammonium acetate aqueous solution as a mobile phase A, takes acetonitrile as a mobile phase B, and adopts a reversed-phase liquid chromatographic column with octadecylsilane bonded silica gel filler as a filler for elution. According to the method, bis (2-chloroethyl) amine can be effectively eluted, separated and quantitatively analyzed, the quality of a cariprazine hydrochloride product can be better controlled, and a simple, convenient, accurate, rapid and reliable detection method is provided for industrial production.

The invention discloses a method for determining potential genotoxic impurities in esomeprazole sodium by HPLC (High Performance Liquid Chromatography), which comprises the following steps: preparing a test solution: taking 20-100mg of esomeprazole sodium, precisely weighing, putting into a 10mL measuring flask, adding methanol, carrying out ultrasonic treatment to dissolve a sample, diluting to a scale by using methanol, and shaking uniformly; a proper amount of 4-methoxy-3, 5-dimethyl pyridine nitrogen oxide is taken, precisely weighed and quantified with methyl alcohol, and the reference substance solution containing 73-360 ng of 4-methoxy-3, 5-dimethyl pyridine nitrogen oxide in 1 mL of the solution is prepared; respectively carrying out HPLC (High Performance Liquid Chromatography) detection on the reference substance solution and the test solution, and determining the content of the impurity 4-methoxy-3, 5-dimethyl pyridine nitrogen oxide in the esomeprazole sodium by adopting an external standard method. The method has the advantages of high separation efficiency, high analysis speed, high detection sensitivity and low detection cost, and can effectively control the quality of esomeprazole sodium.

A highly pure methylene blue is disclosed, as well as a process for preparation and a pharmaceutical composition thereof. In particular, the invention relates to highly pure methylene blue essentially free of impurity N-Nitroso-Azure B. It is also described a methylene blue essentially free of other impurities, such as N-nitrosamines and potentially genotoxic impurities. Additionally it is disclosed the use of said highly pure methylene blue in the treatment of methemoglobinemia. Moreover, it is disclosed a method of analysis to determine the level of N-nitroso-Azure B in the methylene blue or in a pharmaceutical composition comprising the same.

The invention relates to a detection method for toxic impurities of clomacobatel and application, and belongs to the technical field of medicine quality control. The technical problem to be solved is to provide a method for simultaneously separating and detecting four genotoxic impurities, namely p-methyl benzyl chloride, p-(chloromethyl) benzyl alcohol, p-chloromethyl benzaldehyde and p-chloromethyl benzoic acid, from a clomacobamate raw material medicine. The key points of the technical scheme are as follows: chromatographic conditions are as follows: a chromatographic column is a chromatographic column of ion exchange and reverse phase silica gel mixed filler; a mobile phase A is a phosphate buffer solution; a mobile phase B is acetonitrile; the elution conditions are as follows: when the elution time is 0 min, the volume ratio of the mobile phase A to the mobile phase B is 4: 1, 0-30 min, the volume ratio of the mobile phase A to the mobile phase B is changed to 1: 4, 30-35 min, and the volume ratio of the mobile phase A to the mobile phase B is maintained to be 1: 4. The method is good in system applicability, low in detection limit and good in repeatability.

The invention provides a method for detecting a genotoxic impurity o-tolualdehyde in indobufen, which comprises the following steps of: firstly dissolving raw material medicines and then carrying out low-temperature treatment to obtain a test solution with detectable concentration. According to the method, a common ultraviolet detector is used for detection, the method is simple, accurate, efficient and easy to operate, interference of various other organic impurities and genotoxic impurities in the indobufen is avoided, and the problems of high cost and operation complexity caused by pre-column derivatization ultra-high performance liquid chromatography in the prior art are solved.