23 results about "Genotoxic impurities" patented technology

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.

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 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 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 pharmaceutical composition of a nintedanib solution for inhalation. The pharmaceutical composition comprises a first container and a second container, the first container is filled with a first solution, and the first solution contains nintedanib or pharmaceutically acceptable salt thereof and does not contain a nonionic osmotic pressure regulator; the second container is filled with a second solution, and the second solution contains an ionic osmotic pressure regulator and a nonionic osmotic pressure regulator. The medicinal composition disclosed by the invention is simple in component, stable in preparation, capable of avoiding generation of genotoxic impurities, high in safety, lower in irritation to respiratory mucosa and capable of improving the compliance of a patient.

The invention discloses an HPLC (High Performance Liquid Chromatography) method for detecting the content of two genotoxic impurities in phentolamine mesylate, belonging to the technical field of pharmaceutical analysis. The method comprises the following steps: 1) preparing a test solution and a reference solution; 2) setting high performance liquid detection conditions: adopting a chromatographic column taking octadecylsilane chemically bonded silica as a filler, taking an ammonium acetate buffer solution as a mobile phase A, taking acetonitrile as a mobile phase B, and carrying out gradient elution; 3) respectively and precisely sucking the test solution and the reference solution, injecting into a liquid chromatograph, and recording a chromatogram chart.According to the method, the two genotoxic impurities in the phentolamine mesylate can be rapidly, effectively, accurately and reliably separated and detected, the product quality of the phentolamine mesylate is improved, and the medication safety of a patient is further improved.

The invention discloses a method for detecting the content of three potential genotoxic impurities in metoprolol tartrate. The method comprises the following steps: detecting a sample to be detected by adopting gas chromatography-mass spectrometry (GC-MS); the parameter conditions of the gas chromatography are as follows: the temperature of a sample inlet is 210-230 DEG C; the heating procedure is as follows: the initial temperature is 35-45 DEG C, and the temperature is kept for 4-6 minutes; the temperature is raised to 235-245 DEG C at the temperature raising speed of 10-20 DEG C / min, and the temperature is kept for 1.5-2.5 min; headspace parameters are as follows: the temperature of a heating box is 85-95 DEG C; the temperature of a quantitative loop is 120-130 DEG C; the temperature of the transmission line is 125-135 DEG C; the balance time of the headspace bottle is 8-12 min; the sample introduction time is 0.3 to 0.8 min; and the GC circulation time is 25 to 30 minutes. The method disclosed by the invention is simple to operate and high in detection speed, and has the advantages of high sensitivity, high precision and high repeatability.

The invention relates to the technical field of cefotaxime acid impurity control, and particularly discloses a method for controlling genotoxic impurities in cefotaxime acid. Carrying out water quenching and organic solvent extraction on reaction liquid obtained after the reaction of the 7-ACA and the AE active ester, and adjusting the pH value of the obtained water-phase feed liquid to be less than or equal to 7; and then adding a sulfur-loaded adsorbent for adsorption, carrying out solid-liquid separation, and crystallizing the obtained filtrate under an acidic condition to obtain the cefotaxime acid. According to the method provided by the invention, the existing cefotaxime acid synthesis step and crystallization step do not need to be specially set, and the content of 2-mercaptobenzothiazole in the cefotaxime acid product can be ensured to be below 3.0 ppm only by ensuring that the feed liquid before adsorption is an acidic aqueous phase solution and the content of 2-mercaptobenzothiazole in the feed liquid is below 0.5%. The method can be suitable for various cefotaxime acid synthesis processes with a water phase extraction step, is wide in application range, and can realize industrial production.

The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of a high-purity melitracen intermediate 1 and control of genotoxic impurities of the high-purity melitracen intermediate 1. The invention provides a genotoxic impurity A or B, a preparation method thereof and a preparation method of a melitracen intermediate 1. The method has the advantages of high yield, high purity, simple operation and mild conditions, and is suitable for industrial mass production.

The invention relates to a method for detecting genotoxic impurities in vildagliptin and application thereof, and the detection method comprises the following steps: detecting a to-be-detected sample by adopting a liquid chromatography-mass spectrometry method to obtain the content of the genotoxic impurities in the to-be-detected sample. The detection method provided by the invention can realize qualitative and quantitative analysis of genotoxic impurities in vildagliptin, has the advantages of good impurity specificity, good repeatability, high precision and sensitivity, is accurate and reliable, and can be widely applied to detection of the residual quantity of the genotoxic impurities in vildagliptin.

The invention relates to the technical field of drug analysis and detection, and particularly discloses a method for detecting genotoxic impurities in brexpiprazole. According to the method, high performance liquid chromatography is adopted for detection, and chromatographic conditions are as follows: a chromatographic column is a pentafluorophenyl chromatographic column; the detection wavelength is 258-262 nm, a mobile phase A is a phosphate buffer solution with the pH value of 2.0-2.4, a mobile phase B is methanol, and gradient elution is carried out. According to the method, effective separation of brexpiprazole from DDQ and DHQ is achieved, effective control over the quality of the brexpiprazole raw material is facilitated, therefore, the quality of brexpiprazole and the quality of a preparation of the brexpiprazole are guaranteed, monitoring of the synthesis process of the brexpiprazole is facilitated, and the method has very important significance on improvement of medication safety and has high practical value.

The application discloses a method for determining potential genotoxic impurities in levocarnitine by GC-MS, comprising the following steps: preparing a test sample solution: taking 0.2-3g of levocarnitine, accurately weighing, placing in a centrifugal tube, adding 1-2ml of water, shaking to dissolve the sample, adding 5ml of acetone, first shaking to extract, then sealing and centrifuging, and taking the supernatant; preparing a control sample solution; respectively performing GC-MS detection on the control sample solution and the test sample solution, and determining the content of 2,3-dichloro-1-propanol and 1,3-dichloro-2-propanol in the levocarnitine by an external standard method. The application adopts GC-MS to determine the potential genotoxic impurities 2,3-dichloro-1-propanol and 1,3-dichloro-2-propanol in levocarnitine, and has high separation efficiency, fast analysis speed and high detection sensitivity, and can effectively control the quality of the levocarnitine.

The present invention relates to the field of impurities control, in particular genotoxic impurities, in active pharmaceutical ingredients (APIs).In particular, the present invention relates to a packaging method and assembly for the control of the formation of a nitrosamine, for example 1-methyl-4-nitrosopiperazine (MeNP), in a solid active pharmaceutical ingredient (API), for example rifampicin, during storage.

The invention provides a method for detecting genotoxic impurities in a Vonoprazan fumarate preparation, the genotoxic impurities are pyridine ring N-oxides, and the structure of the genotoxic impurities is shown as a formula I. The invention further provides a method for detecting the genotoxic impurities in the Vonoprazan fumarate preparation. The detection method comprises the following steps: mixing a to-be-detected sample with an extraction solvent, performing vortex, performing centrifugation, performing filtration, taking a subsequent filtrate, and performing dilution so as to obtain a test solution; mixing an impurity reference substance with an acetonitrile aqueous solution to obtain a reference substance solution; and performing high performance liquid chromatography detection on the test solution and the reference solution, and determining the content of the genotoxic impurities according to a detection result. The method provided by the invention has the advantages of short peak appearance time, beautiful peak shape, good separation degree, high sensitivity, high accuracy, good durability and the like, is low in quantitation limit and detection limit, can rapidly and effectively detect trace potential genotoxic oxidation impurities in the Vonoprasone fumarate tablets, can efficiently realize quantitative analysis of the oxidation impurities, and has a wide application prospect. The method has important practical significance on the quality control of the fumaric acid Vonoprazan tablets.

The invention discloses a trace detection method for genotoxic impurities in an oral preparation, and belongs to the field of oral preparation detection.The trace detection method comprises the steps that a to-be-detected oral preparation is sampled, an extraction solvent is added and evenly mixed, a sample extracting solution is obtained, and the sample extracting solution is centrifuged or filtered to obtain a sample treatment solution; synchronously shunting the sample treatment liquid according to a preset shunting ratio to obtain a reference branch sample liquid and a capture branch sample liquid, the reference branch sample liquid and the capture branch sample liquid having the same solvent composition and the same treatment time sequence; a reference branch and a capture branch are constructed through synchronous shunting, target genotoxic impurities are selectively removed in the capture branch, and a differential response signal directly represents a net contribution signal of the target impurities, so that co-elution interference under the background of complex auxiliary materials of an oral preparation is inhibited, and the false positive risk is reduced.

The invention relates to a method for detecting p-toluenesulfonate genotoxic impurities in a batyl alcohol bulk drug by gas chromatography-mass spectrometry, and belongs to the technical field of drug analysis and detection. The invention relates to a method for detecting p-toluenesulfonate genotoxic impurities in a batyl alcohol bulk drug by gas chromatography-mass spectrometry. The method comprises the following steps: S1, solution preparation: mixing a standard stock solution; a matrix standard curve solution; a test solution; s2, performing qualitative screening; s3, quantitative calculation: injecting the matrix standard curve solution into a gas chromatography-mass spectrometer for sequential determination, carrying out linear regression by taking a series of concentrations of a to-be-detected component as a horizontal coordinate and a peak area of the to-be-detected component as a vertical coordinate, establishing a standard curve, taking a test solution for determination, substituting a corresponding quantitative ion chromatography peak area into a linear regression equation, and calculating the quantitative ion chromatography peak area of the to-be-detected component. And calculating the content of each component in the sample. The method is high in sensitivity and accuracy, and can be used for simultaneously determining five p-toluenesulfonate genotoxic impurities in the batyl alcohol bulk drug.

The invention belongs to the technical field of pharmaceutical analysis, and particularly relates to a method for separating and determining Enzalocamide Z3 and genotoxic impurities thereof. The impurities comprise one or more of an impurity Xd, an impurity Xg and an impurity Xh. The method comprises the following steps: carrying out linear gradient elution of high performance liquid chromatography by taking octadecyl silane bonded silica gel as a chromatographic column filler, taking a trifluoroacetic acid solution as a mobile phase A and taking acetonitrile as a mobile phase B; and entering a detector for detection. And judging whether the content of each impurity in the sample is qualified or not by adopting a limit method according to the chromatogram. The method disclosed by the invention has the characteristics of good separation degree, good durability, high sensitivity and good reproducibility.

The invention belongs to the technical field of medicines, and particularly relates to a preparation method of a tadalafil nitrosamine impurity. The invention discloses an efficient preparation method of two key nitrosamine impurity compounds of tadalafil. According to the method, nitrosation reaction is performed by adopting a specific reagent, directional synthesis of target impurities is realized under mild and controllable reaction conditions, and the method has the remarkable advantages of simplicity and convenience in operation, high product yield, high purity and the like. According to the method, the problem that related impurities are difficult to obtain is successfully solved, and a key material is provided for toxicological research or qualitative and quantitative research of the tadalafil nitrosamine impurities. The prepared impurity compound can be applied to nitrosamine genotoxic impurity detection and methodological development of tadalafil raw material medicines, preparations and intermediates thereof, and has important value for guaranteeing the safety and compliance of medicines.

The invention discloses a method for controlling and eliminating genotoxic impurities in iguratimod synthesis, and relates to the field of refining processes, and the method comprises the following steps: S1, preparing a ternary composite adsorption material containing a reversible covalent capture group taking porous silica gel as a carrier, a temperature-sensitive cavity inclusion unit and a molecular imprinting recognition site; s2, contacting a crude product reaction solution in the Iguratimod synthesis process with the ternary composite adsorption material, and carrying out adsorption treatment under the conditions that the pH is 5.0-6.0 and the temperature is 20-25 DEG C; according to the method, a ternary composite adsorption material integrating triple functions of reversible covalent capture, thermo-sensitive cavity inclusion and molecular imprinting recognition is designed, so that three types of GTIs of aromatic amine, halogenated hydrocarbon and nitrosamine in a crude product reaction liquid can be synchronously and efficiently removed in one adsorption operation; and a qualified product can be obtained only through one-time standard recrystallization subsequently, so that the production period is greatly shortened, and the production efficiency is improved.