144 results about "Nitrosamine" patented technology

The present invention provides a method for removing a nitrosamine with high selectivity and high efficiency.　More specifically, the present invention provides a method for removing a nitrosamine, the method including a step in which a substance to be irradiated, which contains the nitrosamine, is irradiated with light in the presence of an aromatic polyamine and a photocatalyst.

The invention provides a betahistine hydrochloride pharmaceutical preparation and a preparation method thereof. The betahistine hydrochloride pharmaceutical preparation comprises conjugated linoleic acid, betahistine hydrochloride and auxiliary materials. Conjugated linoleic acid and betahistine hydrochloride are combined together for the first time, and conjugated double bonds of conjugated linoleic acid can be specifically combined with nitrite to block the generation of nitrosamine, so that the content of N-nitrosobetahistine can be remarkably reduced. Based on the chemical characteristics of conjugated linoleic acid, conjugated linoleic acid is used as a functional additive, targeted removal of nitrosamine impurities is achieved, and meanwhile the situation that exogenous toxic substances are introduced to affect the drug effect of betahistine hydrochloride is avoided. In the experiment process, it is also accidentally found that after the conjugated linoleic acid is added, the positive effect on cerebrovascular diseases is also achieved.

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 provides a method for quantitatively detecting a nitrosamine impurity in a macassavir raw material medicine and an intermediate TG9, and relates to the technical field of medicine detection, the method comprises the step of detecting the nitrosamine impurity in the macassavir raw material medicine or the intermediate TG9 sample by adopting a high performance liquid chromatography and mass spectrometry combined method, the mobile phase A is a formic acid solution, and the mobile phase B is a formic acid methanol solution; gradients, such as segmented gradients of the raw material medicines, are respectively designed for the intermediate and the raw material medicines through a dynamic gradient elution program, so that TG801, TG901 and TG1001 realize baseline separation; an acidic mobile phase is adopted, formic acid acetonitrile is added into the solution, protonation competition of nitrosamine impurities is inhibited, the ionization efficiency and stability are improved, the sensitivity is high, and the LOQ of the method is 0.033 ng / g. The technical problem that in the prior art, a method for quantitatively detecting three nitrosamine impurities in a macassavir raw material medicine and an intermediate TG9 does not exist is solved.

The invention provides a UPLC-MS / MS (Ultra Performance Liquid Chromatography-Mass Spectrometry / Mass Spectrometry) detection method for N-nitroso landiolol in a landiolol hydrochloride bulk drug. The method comprises the step of carrying out qualitative detection or quantitative analysis on a potential nitrosamine impurity-N-nitroso landiolol in a landiolol hydrochloride bulk drug by adopting an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS / MS), wherein the structural formula of the N-nitroso landiolol is shown as a formula I in the specification. The detection method disclosed by the invention is high in sensitivity, strong in specificity and good in repeatability, can be used for rapidly and effectively detecting N-nitroso landiolol in the landiolol hydrochloride bulk drug, and has important significance on quality control of the landiolol hydrochloride bulk drug. ; formula I.

The invention discloses a method for determining nitrosamine impurity N-nitrosociprofloxacin in ciprofloxacin lactate, and relates to the field of substance detection methods, the method adopts a liquid chromatography-mass spectrometry technology, and the liquid chromatography condition comprises that a mobile phase is a mixture of a formic acid solution with the concentration of 0.08%-0.12% and acetonitrile, and the volume ratio of the formic acid solution to the acetonitrile is (45-55): (45-55). According to the present invention, the liquid chromatography (LC) technology and the mass spectrometry (MS) technology are combined, such that the efficient separation ability of the liquid chromatography and the high sensitivity detection ability of the mass spectrometry are combined, the detection sensitivity and the detection accuracy are significantly improved, and the strict requirements of drug quality control and safety are met.

The present invention relates to a method for preparing nitrosamine impurities in vonoprazan fumarate, belonging to the technical field of chemical synthesis. By mixing vonoprazan with an organic solvent and reacting the mixture with a nitrosating agent at room temperature, the nitrosamine impurities prepared by this method have a purity exceeding 85%. This method solves the problem of preparing nitrosamine impurities and also provides a reference substance for the study of impurities in vonoprazan fumarate.

The present invention relates to the use of ascorbic acid fatty acid esters for reducing nitrosamine formation in compositions comprising methylphenidate.

Provided are compositions comprising certain miglustat-related nitrosamine compounds, such as pharmaceutical compositions comprising miglustat and such miglustat-related nitrosamine compounds. Also provided are pharmaceutical compositions comprising miglustat and less than certain levels of such miglustat-related nitrosamine compounds. Also provided are methods of analyzing such miglustat-related nitrosamine compounds.

The invention discloses application of acid-producing bacteroides in treatment of hepatic fibrosis and hepatocellular carcinoma. In-vitro cell experiments verify that the Bacteroides acidogenes and the culture medium thereof can inhibit LX2 cell fibrosis induced by TGF-beta, can inhibit the activity of LX2, Huh7 and 97H cells and can inhibit the cell proliferation capacity at the same time, and further, in a hepatocellular carcinoma spontaneous animal model induced by diethylnitrosamine and carbon tetrachloride, the application of the Bacteroides acidogenes and the culture medium of the Bacteroides acidogenes and the culture medium of the Bacteroides acidogenes and the culture medium of the Bacteroides acidogenes in the hepatocellular carcinoma spontaneous animal model has the advantages of being capable of inhibiting the fibrosis of the LX2 cells induced by the TGF-beta and inhibiting the proliferation capacity of the cells. The inhibition effect of the acid-producing bacteroides on hepatic fibrosis and liver cancer progression is verified; the acid-producing bacteroides is recognized as probiotics and has low side effect risk, so that the acid-producing bacteroides has a good clinical application prospect.

A synthetic polyisoprene latex emulsion has pre-vulcanization composition and post vulcanization composition. The pre-vulcanization composition comprises insoluble amorphous sulfur extracted with zinc dithiocarbamate catalyst at 20° C. to form sulfur chain and transported to interior of synthetic polyisoprene particle forming physical attachment of sulfur to active sites. The degree of pre-vulcanization is verified by expansion of cast and dried film of latex in toluene in 20 minutes by means of a swelling index test. The latex emulsion is vulcanized at 90° C. to 120° C. for 3 to 5 minutes. Post-vulcanization composition with accelerators crosslink between synthetic polyisoprene particles, uniformly curing both in the inter-particle and intra-particle regions to produce high cross link density, uniform distribution of double bonds with zinc segregation at the boundaries of original particles. The condom exhibits high tensile strength, tensile modulus, elongation with excellent tear strength releasing below 10 ppb of nitrosamines.

This invention discloses a strain of *Lactobacillus rhamnosus* H7 and its applications, belonging to the field of food microbiology technology. This invention provides a *Lactobacillus rhamnosus* H7 isolated from fermented meat, deposited at the Guangdong Provincial Microbial Culture Collection Center. This strain has the function of degrading nitrite. When inoculated into dried sausage, the residual nitrite and nitrosamine levels in the dried sausage are reduced, and the color of the meat product is significantly improved. When inoculated into fermented mandarin fish, the residual nitrite and nitrosamine levels in the fermented mandarin fish are also reduced. Therefore, inoculating fermented meat products with *Lactobacillus rhamnosus* H7 not only helps improve the safety of fermented meat products but also enhances their quality. This strain has good application prospects as a starter culture for fermented meat products.

The invention relates to a method for determining the content of nitrosamine impurities in a pramipexole dihydrochloride sustained-release tablet, which comprises the following steps: grinding the pramipexole dihydrochloride sustained-release tablet into fine powder as a sample to be detected, and extracting with a diluent to obtain a test solution; and carrying out liquid chromatography-mass spectrometry detection on the test solution, and calculating according to the detection result to obtain the content of the nitrosamine impurity N-nitroso-pramipexole in the pramipexole dihydrochloride sustained release tablet. According to the method, the nitrosamine impurity N-nitroso-pramipexole can be effectively extracted from the pramipexole dihydrochloride sustained release tablet, and the nitrosamine impurity is quantitatively detected by liquid chromatography-mass spectrometry, so that the problems that the nitrosamine impurity N-nitroso-pramipexole is low in content, difficult to detect and easy to interfere are successfully solved. The method is high in accuracy, precision and sensitivity and good in linearity, specificity and system adaptability.

This invention discloses a method for the deamination functionalization of aliphatic nitrosamines, comprising: reacting an aliphatic nitrosamine as shown in formula (II) with a nucleophile in the presence of an acid and a solvent to generate a deamination functionalized product as shown in formula (III); wherein, R 1 R 2 R 3 Each group is independently selected from hydrogen, hydroxyl, alkyl, alkoxy, alkanoyl, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl, aryl, heteroaryl, phenylalkyl, or R 1 R 2 R 3 Two or three of the functional groups form a non-aromatic ring, cage-like compound; FG is a functional group in which a nucleophile participates in the reaction. The method of this invention has the advantages of inexpensive and readily available raw materials, simple reaction conditions, and wide substrate applicability.

The application belongs to the technical field of substance analysis and detection, and provides an extraction method and a detection method for N-nitrosamine compounds in aquatic products. The N-nitrosamine compounds in the aquatic products to be measured are extracted by steam distillation, and the extraction rate of the N-nitrosamine compounds is high. The obtained distillate is purified and enriched by using an acid-modified coconut shell activated carbon column, the acid-modified coconut shell activated carbon column can effectively adsorb N-dimethyl-nitrosamine and N-diethyl-nitrosamine in the distillate, the acid-modified coconut shell activated carbon column is first eluted with n-hexane to remove part of the fat-soluble impurities, then N-dimethyl-nitrosamine and N-diethyl-nitrosamine are eluted with dichloromethane, due to the strong adsorption of the acid-modified coconut shell activated carbon column to the impurities, the impurities are not easily eluted by dichloromethane, so that the impurities, N-dimethyl-nitrosamine and N-diethyl-nitrosamine are effectively separated, and the purpose of purification is achieved.

Provided are compositions comprising certain miglustat-related nitrosamine compounds, such as pharmaceutical compositions comprising miglustat and such miglustat-related nitrosamine compounds. Also provided are pharmaceutical compositions comprising miglustat and less than certain levels of such miglustat-related nitrosamine compounds. Also provided are methods of analyzing such miglustat-related nitrosamine compounds.

This invention discloses a sophoridine tricyclic derivative or its pharmaceutical salt, with the following general structural formula: R1 is selected from hydrogen, C1-C20 straight-chain alkyl, and C1-C20 branched alkyl. In vitro experiments have verified that the sophoridine tricyclic derivative can inhibit TGF-β-induced activation of hepatic stellate cells, improve CCl4- and bile duct ligation-induced liver injury and liver fibrosis in mice, inhibit TGF-β / Smads signaling pathway activation, and also inhibit diethylnitrosamine-induced primary liver cancer in mice. Therefore, this invention provides new evidence for the treatment, alleviation, or improvement of liver fibrosis or primary liver cancer using sophoridine tricyclic derivatives.

The application relates to the technical field of chemical analysis, and discloses a method for extracting, separating and detecting N-nitrosamine, which comprises the following steps: a sample obtaining step; a sample purification step; a preparation and extraction solution step; an extraction solution separation step; an extraction solution concentration step; a chromatographic detection and quantitative analysis step; the sample to be detected is crushed to a size of 0.01g of powder, and the powder is mixed with sodium chloride, barium hydroxide and water. In the application, the sample to be detected is subjected to a step-by-step sample treatment process before detection, so that the interference factors of the sample to be detected can be effectively reduced, the influence on the detection instrument is reduced, the detection result and detection data are more accurate, and when the application is detected, a large amount of sample does not need to be weighed like in the traditional detection mode, the overall operation is more convenient, and the detection demand of N-nitrosamine in smoked food is met.

The invention discloses an epinephrine drug nitrosamine impurity as well as a preparation method and application thereof. According to the method, an epinephrine drug is taken as a raw material, hydroxyl is protected through a silane protecting group, the protected hydroxyl and a nitrosation reagent are subjected to a selective nitrosation reaction, and then the target nitrosamine impurity is obtained through a deprotection reaction. According to the method, the high-purity nitrosamine impurity of the epinephrine medicine can be prepared and used as a reference substance for qualitative and content detection of the nitrosamine impurity in the production process of raw materials and medicines, so that it is ensured that the epinephrine raw material medicine and preparations meet the medicinal standard; the method has important significance in improving the quality of epinephrine drugs and guaranteeing the medication safety.

A process for making a substantially nitrosamine-free, substantially peroxide-free, substantially colorless amine oxide solution comprises reacting a tertiary amine capable of forming an amine oxide with a less than stoichiometric amount of aqueous hydrogen peroxide in an aqueous medium while imposing on the aqueous medium a vapor space having a carbon dioxide partial pressure p(CO2) of less than 0.75 bar absolute. The process allows for obtaining amine oxides which are substantially nitrosamine-free, substantially peroxide-free, and substantially colorless. This unique combination of desirable features has not been achieved so far in a process only comprising oxidation and distillation.

Disclosed are: a pharmaceutical composition capable of inhibiting the generation of a nitrosamine impurity of a vonoprazan drug product by means of an antioxidant; and a preparation method therefor.

The invention relates to the technical field of pharmaceutical analysis, in particular to a method for detecting nitrosamine impurity N-nitrosotrimetazidine in trimetazidine. The invention provides the method for detecting the nitrosamine impurity N-nitroso trimetazidine in the trimetazidine, the detection method has excellent sensitivity, precision, durability and linear relation, and the accurate detection of the N-nitroso trimetazidine in the trimetazidine bulk drug can be met. The method comprises the following steps: detecting a test solution and a reference solution by adopting a liquid chromatography-mass spectrometry method; the gradient elution procedure of the liquid chromatography is as follows: 0.00-2.00 min, and the ratio of a mobile phase A to a mobile phase B is 1: 9; (2.50-3.00) min to (4.00-5.00) min, wherein the ratio of the mobile phase A to the mobile phase B is (3-4.5): (5.5-7); (5.50-6.00) min to (7.00-8.00) min, wherein the ratio of the mobile phase A to the mobile phase B is (4-5): (5-6); and the ratio of the mobile phase A to the mobile phase B is 1: 9.

A method for adsorbing tobacco-specific nitrosamines from a tobacco extract. The method comprises: 1) diluting a tobacco extract with a solvent; 2) adding activated carbon to the diluted tobacco extract, followed by static adsorption; 3) subjecting the tobacco extract, which has been adsorbed by activated carbon, to first centrifugation and then first filtration to obtain a first filtrate; 4) adding a molecular sieve to the first filtrate for stirring and adsorption; 5) subjecting the tobacco extract, which has been adsorbed by the molecular sieve, to second centrifugation and then second filtration to obtain a second filtrate; and 6) concentrating the second filtrate under reduced pressure into a tobacco extract that has been concentrated under reduced pressure having the same solid content as the tobacco extract, wherein the content of tobacco-specific nitrosamines in the tobacco extract that has been concentrated under reduced pressure is less than 70000 ng / g. In addition, a tobacco extract obtained by the method and an atomizing matrix comprising the tobacco extract are provided.

This invention relates to a new process for preparing N-(3-(6-Amino-5-(2-(N- methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2- fluorobenzamide (LOU064) drug substance substantially free of nitrosamine impurities as well as new crystalline forms of salt and solvate of LOU064 used in the process. The invention further relates to pharmaceutical composition comprising N-(3-(6-Amino-5-(2-(N- methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2- fluorobenzamide, wherein the composition is substantially free of a nitrosamine impurity, e.g. the nitrosamine impurity N-(3-(6-amino-5-(2(methyl)(nitroso)amino)ethoxy)pyrimidin-4-yl)-5-fluoro-2- methylphenyl)-4-cyclopropyl-2-fluorobenzamide. Pharmaceutical products containing said drug substance and compositions are also disclosed, as well as methods for preparing said drug substance, pharmaceutical compositions and products.

The invention provides a detection method of nitrosamine impurities in a metformin vildagliptin preparation and application thereof, the detection method comprises the following steps: mixing a to-be-detected sample with a solvent to obtain a test solution, then carrying out liquid chromatography-mass spectrometry detection on the test solution, and determining the content of nitrosamine impurities in the metformin vildagliptin preparation according to the content of nitrosamine impurities in the metformin vildagliptin preparation. And determining the type and / or content of the nitrosamine impurity in the to-be-detected sample according to the detection result. The detection method provided by the invention can qualitatively and quantitatively detect various nitrosamine impurities in the metformin vildagliptin preparation at the same time, has the advantages of high impurity separation degree, good specificity, high precision, good repeatability and high sensitivity, is accurate and reliable, and can be widely applied to quality control of the metformin vildagliptin preparation.

This application discloses an analytical method for N-nitrosamine vortioxetine in vortioxetine hydrobromide tablets, belonging to the field of pharmaceutical impurity analysis. The method employs high-performance liquid chromatography (HPLC), with the following chromatographic conditions: a 4.6 mm × 250 mm column packed with octadecylsilane-bonded silica gel, with a particle size of 5 μm; mobile phase A is a 90:10 water-acetonitrile mixture containing 0.025%–0.035% trifluoroacetic acid (v / v); mobile phase B is acetonitrile; gradient elution; column temperature 38–42 °C; flow rate 0.9–1.1 ml / min; injection volume 50 μl; and detection wavelength 226 nm. This analytical method effectively eliminates excipient interference and exhibits excellent detection performance (specificity, sensitivity, linearity, precision, accuracy, and robustness), accurately detecting the content of N-nitrosamine vortioxetine in vortioxetine hydrobromide tablets, meeting quality control requirements.

The present invention provides an oral composition comprising an Lp(a) inhibitor compound having a reduced level of nitrosamine. [Solution] An oral composition comprising muvalaprin and histidine is used, wherein novel polymorphs of muvalaprin, such as muvalaprin hydrate form A, muvalaprin hydrate form B, muvalaprin hemihydrate, and muvalaprin hydrate 1:6.5 molar equivalents, muvalaprin hemihydrate and / or muvalaprin hydrate 1:6.5 molar equivalents are used. Furthermore, the composition provides a method for treating cardiovascular disease, a method for treating atherosclerotic cardiovascular disease, and / or a method for lowering Lp(a) levels in an individual by administering one of the oral compositions.

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.