81 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 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 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 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 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.

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.

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).

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.

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 benzimidazole derivative as well as a preparation method and application thereof. The benzimidazole derivative has a thiophene-benzimidazole structure and is a compound shown in a structural formula I. In the structural formula I, n is an integer from 0 to 3, R1 is C1-6 alkyl, and R2 is selected from at least one of hydrogen, C1-6 alkyl, C1-6 alkenyl, C1-6 alkynyl, C1-6 alkoxy, C1-6 alkylamino, C1-4 halogenated alkyl and a substituted or unsubstituted pyrazole ring. According to the benzimidazole derivative disclosed by the invention, through a thiophene-benzimidazole structure, the benzimidazole derivative has larger Stokes shift; in addition, no obvious genotoxicity is shown on cells, and gene mutation induction is reduced; the method can be better used for DNA dyeing.

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 photodegradable impurity in a betamethasone sodium phosphate injection as well as a preparation method and a detection method of the photodegradable impurity. The structure of the photodegradation impurity I in the betamethasone sodium phosphate injection is as shown in the following formula I. The impurity has a potential genotoxic structure, can be generated in a large quantity under the illumination condition, can stably exist in a medicine, and seriously affects the quality of the betamethasone sodium phosphate injection. According to the invention, the structure is clarified, so that a clear control standard can be formulated for the impurity, and the impurity can be conveniently monitored and the quality of the betamethasone sodium phosphate injection can be conveniently controlled.

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.

Here, the inventors developed a strategy to modify the chromatin status of HSPCs at the HBG promoters to reactivate HbF expression. In particular, the inventors used from 1 to 4 single guide RNA (sgRNA) molecules spanning from the -220 to the -20 region of the HBG promoters together with CRISPR-based epigenome editors, namely dCas9-CBPcore and Tet1-dCas9. The first editor is capable of inserting histone acetylation while the second editor is performing DNA demethylation. Both epigenetic marks are associated with active transcription and are present in fetal erythroid cells expressing HbF. This strategy allows the ex vivo modification of adult HSCs to recreate a fetal-like epigenetic context leading to HbF production. Moreover, it avoids the genotoxicity associated with classical genome editing tools relying on DNA cleavage. Thus, the present invention relates to a method of increasing the expression of gamma globin in a population of eukaryotic cells through epigenome editing.

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 disclosure provides diagnostic methods, therapeutic methods, compositions and kits for the treatment of cancer. The disclosure is based, at least in part, on the discovery that poorly immunogenic "cold" tumors, which respond poorly to immune checkpoint blockade (ICB) therapy, are strongly associated with impaired TGF0 signaling and error-prone DNA repair, alternative end-joining (alt-EJ). The disclosed methods include approaches for enhancing tumor immunogenicity and overcoming resistance to checkpoint blockade in such cancers with a combination of a genotoxic therapy and inhibition of immunosuppressive cytokines (e.g., TGF0). Selection of suitable cancer patients who are likely to benefit from such therapy are also disclosed, as well as methods of predicting and monitoring therapeutic response.

Acute exposure to estrogenic chemicals is shown herein to induce DNA damage mediated by formation of ERα-dependent R-loops. Disclosed herein are methods for evaluating the safety and activity of a xenoestrogen. Also disclosed are methods for identifying subject particularly susceptible to the genotoxic effects of endogenous estrogens or environmental xenoestrogens. This method can be used to select suitable hormone therapies, such as a selective estrogen receptor modulator (SERM), aromatase inhibitor, or selective estrogen receptor degrader (SERD).

The invention discloses a method for determining potential genotoxic impurities in esomeprazole magnesium by HPLC (High Performance Liquid Chromatography), which comprises the following steps: preparing a test solution: taking 30-90mg of esomeprazole magnesium, precisely weighing, putting into a 10mL measuring flask, adding a proper amount of methanol, dissolving a sample by ultrasonic treatment, diluting with methanol to a scale, and uniformly shaking; preparing a reference substance solution: taking a proper amount of 4-methoxy-2, 3, 5-trimethylpyridine nitrogen oxide, precisely weighing, quantifying with methanol, and preparing the reference substance solution containing 14-170ng of 4-methoxy-2, 3, 5-trimethylpyridine nitrogen oxide in each 1mL of solution; respectively carrying out HPLC (High Performance Liquid Chromatography) detection on the reference solution and the test solution, and determining the content of the genotoxic impurity 4-methoxy-2, 3, 5-trimethylpyridine nitrogen oxide in the esomeprazole magnesium 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.

The application relates to the technical field of pharmaceutical analysis, and particularly discloses a method for detecting genotoxic impurities in moxifloxacin hydrochloride raw materials or preparations. The method is detected by high performance liquid chromatography-mass spectrometry, liquid chromatography conditions are as follows: a C18 chromatographic column is used, a 0.05%-0.2% formic acid aqueous solution is used as a mobile phase A, a 0%-0.2% formic acid acetonitrile solution is used as a mobile phase B, and gradient elution is carried out; the mass spectrometry adopts an ESI ion source, a positive ion detection mode, a parent ion is 431.15 m / z, a daughter ion is 401.18 m / z, and a collision voltage is 10V-25V. The method provided by the application has strong specificity and high sensitivity, the detection limit is 0.625ppm, the blank that the prior art cannot effectively detect N-nitrosomoxifloxacin impurities in moxifloxacin hydrochloride raw materials or preparations is made up, and then the safety risk of moxifloxacin hydrochloride drugs is reduced.

The invention relates to the technical field of medicine refining, in particular to a process for reducing the content of genotoxic impurities in a fluticasone propionate raw material medicine. The process comprises the following steps: S1, reacting a compound I with bromofluoromethane in DMF (Dimethyl Formamide) under an alkaline condition, and adding an adsorbent into an obtained reaction solution; stirring at controlled temperature for a period of time, and filtering at low temperature to obtain fluticasone propionate filtrate; and S2, controlling the temperature at 0-10 DEG C, dropwise adding 1-1.5 mol of hydrochloric acid into the fluticasone propionate filtrate to adjust the pH value and deionized water, filtering, and drying to obtain the fluticasone propionate with reduced genotoxic impurity content. The process for reducing the content of the genotoxic impurities in the fluticasone propionate raw material medicine is simple and convenient to operate and low in cost, not only can reduce the harm of excessive bromofluoromethane to operators, but also greatly reduces the harm of the bromofluoromethane volatilized into the air to the environment, and is very suitable for large-scale industrial application.

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 present application discloses a benzimidazole derivative, a preparation method therefor, and a use thereof. The benzimidazole derivative of the present application comprises a thiophene-benzimidazole structure, and is a compound represented by structural formula I, where n is an integer of 0-3, R1 is a C1-6 alkyl group, and R2 is selected from at least one of hydrogen, a C1-6 alkyl group, a C1-6 alkenyl group, a C1-6 alkynyl group, a C1-6 alkoxy group, a C1-6 alkylamino group, a C1-4 haloalkyl group, and a substituted or unsubstituted pyrazole ring. The benzimidazole derivative of the present application has a larger Stokes shift thanks to the thiophene-benzimidazole structure. Moreover, the benzimidazole derivative of the present application shows no obvious genotoxicity to cells, which reduces induction of gene mutation, allowing it to be better used for DNA staining.

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.