HPLC-MSMS method for determining concentrations of two antitumor drugs in human plasma

An anti-tumor drug, human plasma technology, applied in the direction of measuring devices, instruments, scientific instruments, etc., to achieve the effect of improving accuracy, avoiding adverse reactions, and enhancing selectivity

Active Publication Date: 2019-07-23
SHANGHAI FIRST PEOPLES HOSPITAL
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Problems solved by technology

There is no relevant report about the HPLC-MSMS method of the present invention for measuring the concentration of two antitumor drugs, metabolites and metabolic enzymes related to the activity of endogenous substances in human plasma

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  • HPLC-MSMS method for determining concentrations of two antitumor drugs in human plasma
  • HPLC-MSMS method for determining concentrations of two antitumor drugs in human plasma
  • HPLC-MSMS method for determining concentrations of two antitumor drugs in human plasma

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Embodiment 1

[0049] In this experiment, a detection method based on high-performance liquid chromatography combined with mass spectrometry was used. First, the liquid phase separation was performed on the plasma sample, and then the multiple reaction monitoring (MRM) mode in the mass spectrometer was used, that is, the precursor ion was detected by the quadrupole in the mass spectrometer. Selective screening, the screened ions enter the collision cell for collision fragmentation, and the generated fragment ions are scanned at high resolution, and then the characteristic secondary fragment ions are selected for quantification. And according to the standard curve to calculate the blood concentration of patients.

[0050] 1. Experimental instruments and reagents are as follows:

[0051] Instruments: Chromatographic column: Waters Atlantis T3 (100mm×3.0mm, 3μm), centrifuge, shaker, WATERS2790 liquid mass spectrometer, including WATERS2790 high performance liquid phase, MICRO MASSQU ATTRO tripl...

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Abstract

The invention discloses a method for determining the concentrations of two anti-tumor drugs, metabolites and endogenous substances related to the activity of a metabolic enzyme in human plasma, whichcomprises the following steps: preprocessing, respectively taking voriconazole and bromouracil as internal standards, separating drug components in supernate by using high performance liquid chromatography in a preprocessed sample, performing drug targeting detection by using a high-resolution mass spectrum multi-reaction monitoring mode, and quantifying to realize the analysis and determination of the concentrations of the two anti-tumor drugs, the metabolites and the endogenous substances related to the activity of the metabolic enzyme in the plasma. The method has the advantages of rapidness, extremely high targeting property, high flux, high sensitivity, strong specificity, good precision and accuracy, good stability, high extraction recovery rate, no obvious matrix effect and dilutioneffect and the like. The method for determining the concentrations of two anti-tumor drugs, metabolites and endogenous substances related to the activity of the metabolic enzyme in the human plasma can be used for monitoring the blood concentration of irinotecan and metabolites thereof and the blood concentration of fluorouracil and endogenous substances related to the activity of the metabolic enzyme thereof clinically.

Description

technical field [0001] The invention relates to the technical field of blood drug monitoring, in particular to an HPLC-MSMS method for measuring the concentration of two antitumor drugs, metabolites and metabolic enzymes in human plasma. Background technique [0002] Clinically, irinotecan combined with fluorouracil and calcium folinate is often used as the first-line drug for colorectal cancer. Clinical application In practice, it is found that there are obvious differences in the tolerance of patients to fluorouracil, and the severity of side effects after medication is related to the activity of dihydropyrimidine dehydrogenase (DPD) related to the metabolism of fluorouracil in the patient. DPD enzyme activity can be obtained by measuring the concentration of human endogenous uracil (U) and dihydrouracil (UH2) and calculating the ratio UH2 / U. [0003] Irinotecan (CPT-11) is a semi-synthetic camptothecin derivative, which is metabolized into the main active metabolite 7-et...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/06G01N30/88
CPCG01N30/06G01N30/88
Inventor 范国荣汪硕闻范先煜潘慧张令周利娟秦淑娜王玉勤周金金
Owner SHANGHAI FIRST PEOPLES HOSPITAL
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