Liquid chromatogram-tandem mass spectrum method for detecting pitavastatin in human plasma, and application to clinical pharmacokinetic research

Abstract

The invention relates to a liquid chromatogram-tandem mass spectrum method for detecting pitavastatin in human plasma, and application to clinical pharmacokinetic research. The invention provides a method for detecting pitavastatin concentration of plasma. By the method, the pitavastatin concentration of the plasma can be analyzed through LC-MS / MS. According to the method provided by the invention, a protein precipitate pretreatment method is preferably adopted, deuterated pitavastatin serves as internal standard, Eclipse Plus Phenyl-Hexyl column isocratic elution is adopted, and electrospray ionization (ESI) tandem mass spectrum detection is adopted. By adoption of the method provided by the invention, the extraction and recovery rate of the plasma sample is 93 percent or higher and is not influenced by matrix effect, the stability of the pitavastatin is inspected by counting the pitavastatin concentration RSD% before pretreatment, the accuracy of the measured data is guaranteed, the method is high in specificity and selectivity, high in sensitivity, rapid in detection and small in use amount, and simple, reliable, high-flux and condition-controllable clinical mass-batch sample analysis requirements are met. The specificity, the stability and the like of the method provided by the invention are verified, and the method can be used for evaluating the bioequivalence of various dosage forms of pitavastatin successfully.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a liquid chromatography-tandem mass spectrometry method for detecting pitavastatin in human plasma and an application thereof. Background technique [0002] Pitavastatin (Pitavastatin, PTV) structural formula is as follows figure 1 As shown, it is a third-generation statin drug jointly developed by Nissan Chemical Industry Co., Ltd. and Kowa Co., Ltd., which is a kind of inhibitor of hydroxymethylglutaryl coenzyme A (HMG-CoA), which can effectively reduce blood lipid levels. It is clinically used to treat primary hyperlipidemia and mixed dyslipidemia. PTV exists mainly in the form of the original form in the human body, just like other statin compounds. The PTV structure contains a hydroxycarboxylic acid structure, which can be dehydrated and ring-closed to form a pitavastatin lactone structure both in vivo and in vitro. Since pitavastatin lactone is easily hyd...

AI Technical Summary

Problems solved by technology

[0006] In order to solve the above technical problems, in order to establish a simple, reliable, high-throughput, condition-controllable extraction and detection of protein precipitation method, and use deuterated internal standard as calibration for the determination of the plasma concentration of pitavastatin in human plasma, To solve the problems of long analysis period of biological samples, complex pretreatment, unstable drugs, etc.

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