161 results about "Genotoxicity" patented technology

The invention provides a method for detecting a genotoxic impurity TG707 in a macassavir raw material medicine and an intermediate TG7, and relates to the technical field of medicine detection, and the method comprises the step of detecting the genotoxic impurity TG707 in the macassavir raw material medicine or the intermediate TG7 sample by adopting a high performance liquid chromatography and mass spectrometry combined method, the mobile phase A is an ammonium acetate solution, and the mobile phase B is methanol. By adopting a liquid chromatography-mass spectrometry method and utilizing the selectivity of mass spectrum multi-channel monitoring, main components and impurities enter mass spectrum at the same time, the interference of high-concentration main components on the mass spectrum detection sensitivity is avoided, good separation on the mass spectrum is realized, and the sensitivity is relatively high; an ammonium acetate solution and methanol are used as mobile phases, so that the peak pattern and sensitivity of TG707 are ensured. The technical problems that in the prior art, the peak of TG707 on a liquid phase is between two peaks of a main component TG7, and baseline separation is difficult to achieve by replacing a chromatographic column and optimizing the fluidity gradient are solved.

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 invention relates to the technical field of medicines, relates to a preparation method and application of a genotoxic impurity standard substance in acarbose, and in particular relates to a preparation method and application of a genotoxic impurity N-nitrosyl acarbose in an acarbose tablet. According to the method, the nitrosamine new structure compound NNA is prepared for the first time, the genotoxic impurity NNA with high purity can be effectively prepared through the method, the blank of an impurity preparation method at present is filled, the preparation process is simple, and a large number of high-purity NAA impurity standard substances can be prepared. The invention provides a UHPLC-Orbitrap-HRMS (Ultra High Performance Liquid Chromatography-Orbitrap-High Resolution Mass Spectrometry) combined technology, so that the quality control of the NNA in the acarbose tablet is effectively realized, the side reaction of medication is reduced, and the medication safety is ensured to a certain extent. Meanwhile, reference is provided for quality evaluation of other starting materials or intermediates capable of generating NNA.

The invention relates to an animal genetic toxicity experiment technology, and discloses an animal micronucleus cell auxiliary detection method and system based on deep learning, and the method comprises the steps: making an animal micronucleus image data set through a provided animal micronucleus test slide; constructing a network model of an animal micronucleus cell assisted detection algorithm based on deep learning for the manufactured animal micronucleus data set; enriching target information extracted by a backbone network through dynamic convolution for a network model constructed according to the animal micronucleus data set; carrying out convolution operation through a wavelet convolution layer so as to optimize the network model; and after the training is finished, testing the network model through the test set, and evaluating the performance of the network model. The target detection technology based on deep learning is gradually applied to the medical field, targets needed by medical staff can be rapidly screened out, the efficiency is improved, meanwhile, manpower waste is reduced, and a novel cell micronucleus visual analysis and detection strategy shows a good application prospect.

The present invention relates to a stable pharmaceutical formulation comprising linagliptin or pharmaceutically acceptable forms or derivatives thereof and at least one pharmaceutically acceptable excipient is obtained wherein the manufacturing method is direct compression method, wherein the composition is free of any nitrosamine impurity.

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 present invention belongs to the field of pharmaceutical and chemical engineering, and relates to a high-purity losartan potassium and a preparation method therefor. The present invention also relates to a high-purity losartan or a pharmaceutically acceptable salt thereof and a preparation method therefor. The present invention uses organic phosphorus to reduce an azide compound to an amino compound so that the genotoxicity of losartan or a pharmaceutically acceptable salt thereof can be well controlled. The method of the present invention involves fewer steps, uses a small amount of reagent, does not require activated carbon decolorization, and produces a high-purity product, and therefore is suitable for industrial production and is very practical.

The invention relates to the technical field of analytical chemistry, and particularly discloses an HPLC (High Performance Liquid Chromatography) detection method of propranolol hydrochloride genotoxic impurity 1-naphthylamine and application of the HPLC detection method. The HPLC detection method for the propranolol hydrochloride genotoxic impurity 1-naphthylamine provided by the invention comprises the following steps: preparing a reference substance solution, preparing a test solution, and carrying out liquid chromatography detection, liquid chromatography detection: injecting the reference substance solution and the test solution into a liquid chromatograph, and carrying out separation detection by adopting a mobile phase gradient elution method; a used chromatographic column is a chromatographic column with octadecylsilane chemically bonded silica as a filler. The HPLC detection method of the propranolol hydrochloride genotoxic impurity 1-naphthylamine provided by the invention can rapidly and accurately detect the genotoxic impurity 1-naphthylamine in a propranolol hydrochloride bulk drug or a propranolol hydrochloride injection, and has the advantages of good detection accuracy, high sensitivity, good reliability and high detection sensitivity. And the quality control of propranolol hydrochloride bulk drugs or injections can be realized.

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 relates to the use of a compound of Formula (I) as described herein and its effective dose in the prevention and / or treatment of fibrosis diseases. The compound can effectively prevent and / or treat a fibrosis disease without cytotoxicity or genotoxicity.

The invention belongs to the technical field of medicine synthesis, and discloses a bisacodine genotoxic impurity and a preparation method and application thereof.The bisacodine genotoxic impurity is specifically bisacodine nitric oxide, and the preparation method comprises the following steps that bisacodine serves as a raw material and is oxidized through an oxidizing agent; extracting with ethyl acetate, collecting an ethyl acetate layer, and concentrating under reduced pressure. The invention successfully confirms the structure of bisacodine nitrogen oxide, the provided preparation method has the characteristics of simple operation, common and easily available raw materials, mild reaction conditions, no high-temperature and high-pressure step, thorough conversion of reaction raw materials, high yield and the like, and the obtained product has high purity, can be used as a reference substance for quality control of bisacodine raw materials and preparations, and has wide application prospects. And a guarantee is provided for safe medication of the bisacodine.

The invention discloses a method for preparing phenylephrine hydrochloride genotoxic impurities, which comprises the following steps: by taking 3-hydroxyacetophenone as a starting material and copper bromide as a bromine source in isopropanol, reacting, and then preparing and separating to obtain dibromide impurities. The reaction condition for preparing the phenylephrine hydrochloride genotoxic impurity is mild, the operation is simple, the product purity is high, and the quality requirement for controlling phenylephrine hydrochloride can be met.

The invention relates to a spherical crystal of a medicinal crystal form B of nilotinib hydrochloride and a preparation method of the spherical crystal. According to the method, nilotinib hydrochloride is used as a substrate, and a methanol-water binary solvent is used as a solvent system; the crystal form prepared by the method is uniform in particle size distribution and controllable in size, genotoxic impurities can be stably controlled below 3ppm, the inherent dissolution is obviously improved, and the bioavailability is favorably improved.

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 belongs to the field of medicine quality control, and particularly relates to a method for detecting N-nitroso-deethylidocaine genotoxic impurities in lidocaine. The method is realized by the following steps: firstly, preparing a test solution and a reference solution; and then, detecting by adopting a high performance liquid chromatography-triple quadrupole mass spectrometry method. The detection method provided by the invention can realize good quality control on lidocaine raw material medicines and preparations thereof, is strong in durability and high in detection sensitivity, can effectively avoid interference generated by a solvent, has a good impurity separation effect, can accurately detect toxic impurities in lidocaine, and is suitable for large-scale popularization and application. The method has the advantages of high sensitivity, strong specificity and good reproducibility. The detection method provided by the invention is simple and strong in operability.

The present invention relates to amino naphthoquinone compounds for the treatment and / or prophylaxis of fibrous diseases. The present invention relates to the use of compounds of formula (I) as described herein and effective doses thereof in the prevention and / or treatment of fibrous diseases. The compound can effectively prevent and / or treat fibrotic diseases without cytotoxicity or genotoxicity.

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 a detection method for determining N-methylpiperazine in clozapine, and belongs to the technical field of drug detection, the detection method comprises solution preparation and detection; in the step of preparing the solution, clozapine is used for preparing a test solution, and N-methyl piperazine is used for preparing a reference solution; the detection comprises the following steps: determining the test solution and the reference solution by adopting a liquid chromatography-mass spectrometry method, recording a chromatogram, and calculating the content of N-methyl piperazine; in the detection, the conditions of liquid chromatography are as follows: a mobile phase is composed of a mobile phase A and a mobile phase B, and the mobile phase A is an aqueous solution of 0.048-0.052% trifluoroacetic acid; the mobile phase B is acetonitrile; according to the method, the genotoxic impurity N-methylpiperazine in the clozapine raw material medicine and the preparation can be quantitatively detected, the content of the impurity in the clozapine production and storage process can be conveniently monitored, the selectivity is high, the sensitivity is good, and the limit of quantitation can be as low as 0.165 ppm.

In the field of gene therapy, a major hurdle is the design and identification of constructs and gene therapy vectors providing therapeutic effects while displaying satisfactory safety profiles. In the treatment of Diamond-Blackfan Anemia (DBA), therapies alleviating several crucial anemia symptoms, such as blood or bone marrow cellularity, hemoglobin levels, erythrocytes levels, or platelet levels, while showing satisfactory safety profiles remain a challenge. The present invention provides constructs encoding ribosomal protein genes involved in DBA, such as genes encoding RPS19, RPS17, RPS24, RPS10, RPL35a, RPL11, RPS26, and RPL5, vectors, methods, cells, and medical uses thereof, addressing these challenges and finding particular applications in the field of autologous cell therapy treatment of DBA. Further, the present invention provides a non-genotoxic conditioning protocol for preparing a subject prior to cell therapy treatment for DBA using construct of the present invention.

The invention relates to a construction method and application of a marine micro-plastic ecological risk assessment model based on a multilevel toxicity effect, and belongs to the technical field of ecological risk assessment of marine pollutants. According to the method, a toxicity end point sensitive to exposure of the microplastics is determined by screening research results of the microplastics on toxicity effects of marine organisms at different levels, and non-effect concentration is deduced and predicted by adopting a species sensitivity distribution model. The ecological risk of micro-plastic pollution in the marine water environment is determined according to the environmental concentration of the micro-plastic and the PNEC of the micro-plastic to marine organisms. According to the method, the ecological risk of the micro-plastics is evaluated from multiple levels, and the ecological risk of the micro-plastics to marine organisms can be pre-judged in advance. When it is detected that the microplastic with pathological damage, oxidative stress, metabolic toxicity and genotoxicity is in a high-risk state, intervention needs to be performed in advance to prevent the risk from being further expanded to affect individuals and populations of marine organisms.

This application relates to the technical field of biomedical detection, and specifically discloses a method for detecting the content of the genotoxic impurity 6-chloro-2-hexanone in pentoxifylline raw materials and injection solutions. The detection method disclosed in this application uses gas chromatography-mass spectrometry (GC-MS) to detect samples; the gas chromatography parameters are: injection port temperature 190 - 210 °C; temperature programming: initial temperature 75 - 85 °C, heated to 150 - 170 °C at a rate of 15 - 25 °C / min, held for 1.5 - 2.5 min, then heated to 210 - 230 °C at a rate of 55 - 65 °C / min, held for 1.5 - 2.5 min; the mass spectrometry parameters are: solvent delay 3 - 4 min; transfer line temperature 240 - 260 °C; quadrupole temperature 140 - 160 °C; ion source temperature 240 - 260 °C. The method of this application is simple to operate, has a fast detection speed, and has the advantages of high sensitivity, high precision, and high repeatability.

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 present application relates to aziridine-functional compounds with reduced genotoxicity and good cross-linking efficiency, which are useful for preparing, for example, coatings.

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 present invention proposes a method for detecting piperonyl chloride in dopamine hydrochloride and a method for quality control of dopamine hydrochloride. The detection method comprises: using a gas chromatography-mass spectrometer to detect a dopamine hydrochloride sample to be detected; wherein the detection is performed by split injection, constant flow of carrier gas and programmed temperature rise. The detection method of the present invention can effectively separate and detect piperonyl chloride, has the advantages of high accuracy, good separation, low detection limit, good applicability, durability and specificity, simple and fast operation, high efficiency, etc., and is suitable for wide application.

Described herein is an adeno-associated virus (AAV) complex platform including an asymmetrically modified inverted terminal repeat (ITR). The AAV complex has advantages of increased productivity and expression efficiency of a transgene, and decreased genotoxicity, by having an asymmetric ITR in which any one of two ITRs is modified. Also, described herein is a composition comprising the adeno-associated virus complex and a method of gene therapy.

The invention provides a method for detecting the genetic toxicity of nitrosamine compounds, and belongs to the technical field of biological detection. According to the method, key conditions of a detection system are systematically optimized, so that the detection sensitivity and the result reliability of the genotoxicity of the nitrosamine compounds are remarkably improved, and the mutagenicity which is difficult to detect under conventional conditions can be stably and clearly identified; the establishment of the method provides powerful technical support for early screening and safety risk assessment of nitrosamine impurities in drugs and chemicals, and has important practical application value for guaranteeing medication safety and product quality.