Chiral LC-MS (liquid chromatograph-mass spectrometer)/MS high-throughput detection method for pantoprazole in human plasma

Abstract

The invention relates to a chiral LC-MS (liquid chromatograph-mass spectrometer) / MS high-throughput detection method for pantoprazole in human plasma. The method includes the steps: taking plasma samples to be detected to mix into internal standard solution; adding 500muL internal standard solution into the plasma samples to serve as protein precipitators by the aid of a pretreatment method of a protein precipitation method; taking liquid supernatant after vortex and centrifugation to obtain samples to be detected; performing LC-MS analysis. The method has the advantages that the method meets analysis requirements of large-batch clinical samples and is simple to operate, short in pretreatment time and chromatographic analysis time and suitable for pretreatment of high-throughput samples as compared with the prior art.

Description

technical field [0001] The invention relates to an analysis and detection method for pantoprazole and its enantiomers in biological samples, in particular to a chiral LC-MS / MS high-throughput detection method for pantoprazole in human plasma. Background technique [0002] Chiral drugs refer to a pair of enantiomers that are real objects and mirror images obtained after introducing a chiral center into the molecular structure of a drug. There may be great differences in their pharmacodynamics, pharmacokinetics and toxicology. For example, proton pump inhibitors have similar structural characteristics, and there is a mixture of a pair of enantiomers with a chiral sulfur atom center in the molecule. , the pharmacodynamics and pharmacokinetics of such drugs exhibit enantiomeric differences. The common problem with existing technologies is that most technologies only quantify the racemates of proton pump inhibitors such as pantoprazole, and rarely quantify their individual enant...

AI Technical Summary

Problems solved by technology

The common problem with existing technologies is that most technologies only quantify the racemates of proton pump inhibitors such as pantoprazole, and rarely quantify their individual enantiomers, and most technologies do not use deuterated internal standards , which affects the accuracy and reproducibility of the analysis, and some methods use liquid chromatography-ultraviolet detection technology. The sensitivity of this technology cannot meet the requirements of low-dose human pharmacokinetic studies. Liquid chromatography-tandem mass spectrometry (LC-MS / MS) detection technology, but due to the small structural differences between the corresponding isomers, chromatographic separation often takes a long time, which greatly reduces the efficiency of the analysis, and is not suitable for the analysis of the number of easily Analysis of thousands of large batches of clinical samples

[0003] At present, there are two main technologies for chiral detection of S-(-)-pantoprazole and R-(+)-pantoprazole in plasma, namely liquid chromatography-ultraviolet technology and liquid chromatography-tandem mass spectrometry , because liquid chromatography-ultraviolet technology requires a very long chromatographic separation time, the amount of analyzed samples per day is less than 50, which greatly limits the analysis throughput, and the sensitivity is poor. The lower limit of quantification is usually above 100ng / mL, which cannot meet the current pan Therefore, it is urgent to develop a simple, rapid and high-precision sample pretreatment method, combined with LC-MS / MS chromatography technology, to shorten the running time and achieve high throughput

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