Sep 2021 News Final Thoughts on Chemistry for Atorvastatin lactone

Balanced chemical reaction does not necessarily reveal either the individual elementary reactions by which a reaction occurs or its rate law.COA of Formula: C33H33FN2O4. In my other articles, you can also check out more blogs about 125995-03-1

Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps. 125995-03-1, Name is Atorvastatin lactone, molecular formula is C33H33FN2O4. In a Article,once mentioned of 125995-03-1, COA of Formula: C33H33FN2O4

A rapid, sensitive and selective ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of atorvastatin and all its as-yet-identified metabolites in human plasma. Atorvastatin, its metabolites, and the internal standard (IS) were isolated from human plasma by liquid-liquid extraction with ethyl acetate and then separated on an Acquity UPLC HSS T3 column (3.0 mm × 100 mm, 1.8 mum) using 0.05% (v/v) formic acid in water/acetonitrile (25?:?75, v/v) as the mobile phase. Atorvastatin and all five metabolites were eluted within 4 min. Quantification was performed through positive ion electrospray ionization (ESI). The responses of atorvastatin and its metabolites ortho-hydroxy atorvastatin, para-hydroxy atorvastatin, atorvastatin lactone, ortho-hydroxy atorvastatin lactone, and para-hydroxy atorvastatin lactone were optimized at the m/z 559.4 ? 440.1, m/z 575.4 ? 466.2, m/z 575.5 ? 440.5, m/z 541.3 ? 448.3, m/z 557.3 ? 448.3, and m/z 557.3 ? 448.3 transitions, respectively. The assay was validated in the linear range of 0.2-40 ng mL?1 for atorvastatin and its metabolites. The intra- and inter-day precision variations were between 3.3% and 13.9%. The matrix effects of plasma were in the range of 102.7-105.5% for atorvastatin and 90.3-96.6% for atorvastatin lactone. This method was successfully applied in clinical studies of atorvastatin in coronary artery disease patients.

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Cardiovascular disease is a leading cause of morbidity, mortality, and healthcare expenditure worldwide. Importantly, there is interindividual variation in response to cardiovascular medications, leading to variable efficacy and adverse events. Therefore a rapid, selective, sensitive and reproducible multi-analyte HPLC-MS/MS assay for the quantification in human plasma of atorvastatin, its major metabolites 2-hydroxyatorvastatin, atorvastatin lactone and 2-hydroxyatorvastatin lactone, plus bisoprolol and clopidogrel-carboxylic acid has been developed, fully validated, and applied to a large patient study. Fifty microliter plasma samples were extracted with a simple protein precipitation procedure involving acetonitrile with acetic acid (0.1%, v/v). Chromatographic separation was via a 2.7 mum Halo C18 (50 × 2.1 mm ID, 90 A) column and gradient elution at a flow rate of 500 muL/min consisting of a mobile phase of water (A) and acetonitrile (B), each containing 0.1% formic acid (v/v), over a 6.0 min run time. The six analytes and their corresponding six deuterated internal standards underwent positive ion electrospray ionisation and were detected with multiple reaction monitoring. The developed method was fully validated with acceptable selectivity, carryover, dilution integrity, and within-run and between-run accuracy and precision. Mean extraction recovery for the analytes was 92.7?108.5%, and internal standard-normalised matrix effects had acceptable precision (coefficients of variation 2.2?12.3%). Moreover, all analytes were stable under the tested conditions. Atorvastatin lactone to acid interconversion was assessed and recommendations for its minimisation are made. The validated assay was successfully applied to analyse 1279 samples from 1024 patients recruited to a cardiovascular secondary prevention prospective study.

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Redox catalysis has been broadly utilized in electrochemical synthesis due to its kinetic advantages over direct electrolysis. The appropriate choice can avoid electrode passivation, which strongly inhibit the efficient activation of substrates. 125995-03-1, Name is Atorvastatin lactone, molecular formula is C33H33FN2O4. In a Patent,once mentioned of 125995-03-1, Product Details of 125995-03-1

Atorvastatin lactone is prepared by hydrogenating tert-butyl isopropylidene nitrile to tert-butyl isopropylidene amine and condensing the amine with the diketone of atorvastatin to form acetonide ester. The diol protecting acetonide ester is deprotected to form a diol ester by dissolving the acetonide ester in methanol and treating with an acid. The diol ester is saponified to form a sodium salt. Methanol is removed from the reaction mixture by distillation. The sodium salt is reacidified to the free diol acid and atorvastatin lactone is formed from the diol acid. The atorvastatin lactone is directly dried without further purification.

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Catalysts allow a reaction to proceed via a pathway that has a lower activation energy than the uncatalyzed reaction. In homogeneous catalysis, catalysts are in the same phase as the reactants.125995-03-1, C33H33FN2O4. A document type is Article, introducing its new discovery., Formula: C33H33FN2O4

A concise and convergent synthesis of the atorvastatin, the best-selling cardiovascular drug of all time, is presented. Our approach is based on an Ugi reaction, which shortens the current synthetic route and is advantageous over the published syntheses.

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In individuals, heterogeneous drug-response phenotypes result from a complex interplay of dose, drug specificity, genetic background, and environmental factors, thus challenging our understanding of the underlying processes and optimal use of drugs in the clinical setting. Here, we use mass-spectrometry-based quantification of molecular response phenotypes and logic modeling to explain drug-response differences in a panel of cell lines. We apply this approach to cellular cholesterol regulation, a biological process with high clinical relevance. From the quantified molecular phenotypes elicited by various targeted pharmacologic or genetic treatments, we generated cell-line-specific models that quantified the processes beneath the idiotypic intracellular drug responses. The models revealed that, in addition to drug uptake and metabolism, further cellular processes displayed significant pharmacodynamic response variability between the cell lines, resulting in cell-line-specific drug-response phenotypes. This study demonstrates the importance of integrating different types of quantitative systems-level molecular measurements with modeling to understand the effect of pharmacological perturbations on complex biological processes. Blattmann et al. combine proteomic and metabolomic profiling with mechanistic modeling to characterize the complex processes underlying the heterogeneous drug response in cellular cholesterol regulation across a panel of different human cell lines.

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The reactant in an enzyme-catalyzed reaction is called a substrate. Enzyme inhibitors cause a decrease in the reaction rate of an enzyme-catalyzed reaction.I hope my blog about 125995-03-1 is helpful to your research., Safety of Atorvastatin lactone

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An efficient strategy for the synthesis of syn 1,3-diol has been developed, employing an imidazolidinone based chiral auxiliary via stereoselective and sequential double acetate aldol reactions. The syn 1,3-diol subunit was modified to obtain the C-7 carboxylic acid side chain and further subjected to reaction with a suitable 1,4-diketone under Paal-Knorr conditions to obtain atorvastatin lactone.

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The present invention relates to the field of medicine, specifically the field of treatment and prevention of cardiovascular diseases.

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Impurities will be present in all drug substances and drug products, i.e. nothing is 100% pure if one looks in enough depth. The current regulatory guidance on impurities accepts this, and for drug products with a dose of less than 2 g/day identification of impurities is set at 0.1% levels and above (ICH Q3B(R2), 2006). For some impurities, this is a simple undertaking as generally available analytical techniques can address the prevailing analytical challenges; whereas, for others this may be much more challenging requiring more sophisticated analytical approaches. The present review provides an insight into current development of analytical techniques to investigate and quantify impurities in drug substances and drug products providing discussion of progress particular within the field of chromatography to ensure separation of and quantification of those related impurities. Further, a section is devoted to the identification of classical impurities, but in addition, inorganic (metal residues) and solid state impurities are also discussed. Risk control strategies for pharmaceutical impurities aligned with several of the ICH guidelines, are also discussed.

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Atorvastatin belongs to the group of lipid-lowering drugs known as statins. They significantly reduce the levels of total cholesterol, low-density cholesterol and plasma triglycerides therefore they are widely used in the treatment of hypercholesterolemia. Recently developed methods for the determination of atorvastatin and its metabolites in plasma used SPE (solid phase extraction) or LLE (liquid-liquid extraction) as the sample preparation step. However, both procedures are quite time-consuming and need relatively high volume of solvent/sample, which is impractical for the routine analyses of many biological samples.The aim of this work was to develop and validate more suitable sample preparation method for the determination of atorvastatin and its metabolites in biological samples using MEPS (microextraction by packed sorbent). The optimal conditions of MEPS extraction were using C8 sorbent and only 50mul of the sample. The analytes were eluted by 100mul of the mixture of acetonitrile:0.1M ammonium acetate pH 4.5 (95:5, v:v). The analytical method was validated and demonstrated good linearity (r2>0.9990), recovery (89-115%) and intra-day precision (RSD<10%). Total time of the sample preparation was three times shorter (7min) compared to SPE. The volume of sample was twenty times lower and the volume of solvents about ten times lower compared to SPE. Combination of fast MEPS method together with quick UHPLC-MS/MS was used for the determination of atorvastatin and its two metabolites in serum obtained from patients with familiar hypercholesterolemia. The proportionality constant is the rate constant for the particular unimolecular reaction. the reaction rate is directly proportional to the concentration of the reactant. I hope my blog about 125995-03-1 is helpful to your research., Application of 125995-03-1

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The drug?drug interaction profile of atorvastatin confirms that disposition is determined by cytochrome P450 (CYP) 3A4 and organic anion transporting polypeptides (OATPs). Drugs that affect gastric emptying, including dulaglutide, also affect atorvastatin pharmacokinetics (PK). Atorvastatin is a carboxylic acid that exists in equilibrium with a lactone form in vivo. The purpose of this work was to assess gastric acid?mediated lactone equilibration of atorvastatin and incorporate this into a physiologically-based PK (PBPK) model to describe atorvastatin acid, lactone, and their major metabolites. In vitro acid-to-lactone conversion was assessed in simulated gastric fluid and included in the model. The PBPK model was verified with in vivo data including CYP3A4 and OATP inhibition studies. Altering the gastric acid?lactone equilibrium reproduced the change in atorvastatin PK observed with dulaglutide. The model emphasizes the need to include gastric acid?lactone conversion and all major atorvastatin-related species for the prediction of atorvastatin PK.

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