Method for measuring concentration of molecular targeted drugs in plasma by using ultra-high performance liquid chromatography tandem mass spectrometry
An ultra-high performance liquid chromatography and tandem mass spectrometry technology, which is applied in the field of ultra-high performance liquid chromatography tandem mass spectrometry to determine the concentration of plasma molecular targeted drugs, and achieves the effects of strong specificity, good reproducibility and high sensitivity
Inactive Publication Date: 2019-08-02
BEIJING CHAOYANG HOSPITAL CAPITAL MEDICAL UNIV
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The determination of various molecularly targeted drugs by high performance liquid chromatography tandem mass spectrometry is not easy to achieve by simply adjusting the instrument parameters. How to ensure that the analytes do not interfere with each other is a difficult problem in quantitative analysis, which is why there is no such method currently used. Chromatography tandem mass spectrometry is the reason for the disclosure of the technology for the simultaneous detection of multiple anti-tumor molecular targeted drugs
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[0034] 1 solution preparation
[0035] The volumes and weights used to prepare solutions can be adjusted proportionally, and all solutions are stored at room temperature unless otherwise stated.
[0036] 1.1 Preparation of mobile phase solution
[0037] Organic phase (A): Methanol containing 0.2% formic acid and 5 mM ammonium acetate by mass fraction.
[0038] Aqueous phase (B): water containing 0.2% formic acid and 5 mM ammonium acetate by mass fraction.
[0039] Mobile phase selection: In order to meet the requirements of low quantitative detection range in the experiment, we investigated the organic phase (such as methanol, acetonitrile, etc.) and aqueous phase in various commonly used mobile phases, and tried to add different proportions of solution enhancers (such as 0.01 % formic acid, 0.05% formic acid, 0.2% formic acid, 0.01% acetic acid, 2mM ammonium formate, 5mM ammonium formate, 2mM ammonium acetate, etc.). It was found that when formic acid was added to the orga...
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The invention discloses a method for measuring the concentration of molecular targeted drugs in plasma by using ultra-high performance liquid chromatography tandem mass spectrometry. The method comprises the following steps of respectively dissolving anlotinib, ceritinib and ibrutinib by adopting acetonitrile in order to prepare a standard curve working solution, and dissolving diazepam by adopting methanol in order to prepare an internal standard substance working solution; respectively adding 0-5 microliters of standard curve working solution into blank plasma to make up to 50 microliters, carrying out vortex to prepare a standard curve plasma sample, adding the internal standard substance working solution, carrying out vortex and centrifugation, taking supernate, carrying out UPLC-MS/MSquantitative analysis, and drawing a standard curve; and precisely sucking to-be-detected plasma with the concentration of 50 microliters, adopting the same sample pretreatment method, and measuringthe concentration of the anlotinib, the ceritinib and the ibrutinib according to a standard curve of the batch. According to the method, the blood concentration of various anti-tumor molecular targeted drugs can be measured simultaneously, the method is high in sensitivity, strong in specificity, rapid and good in reproducibility and is suitable for clinical high-throughput simultaneous detectionand monitoring of various anti-tumor molecular targeted drugs.
Description
technical field [0001] The present invention relates to methods for detecting drug concentrations. More specifically, the present invention relates to a method for determining the concentration of plasma molecular targeted drugs by ultra-high performance liquid chromatography tandem mass spectrometry. Background technique [0002] Anlotinib is one of the original innovative drugs in China. It is a new type of small molecule multi-target tyrosine kinase inhibitor, which can effectively inhibit VEGFR, PDGFR, FGFR, c-Kit and other kinases. It has anti-tumor vascular It has dual effects of generating and inhibiting tumor growth, and was approved for marketing by the State Drug Administration in May 2018. Ceritinib is a new type of potent and selective small molecule ATP-competitive ALK receptor tyrosine kinase inhibitor, which was approved by the FDA in April 2014 for the treatment of ALK-positive or crizotinib-resistant patients. For non-small cell lung cancer (NSCLC), the 20...
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IPC IPC(8): G01N30/02G01N30/72
CPCG01N30/02G01N30/72
Inventor 杜萍刘丽宏
Owner BEIJING CHAOYANG HOSPITAL CAPITAL MEDICAL UNIV
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