Method for simultaneously determining eight antituberculous drugs in human plasma based on LC-MS

Abstract

The invention belongs to the technical field of analytical chemistry, and particularly relates to a method for simultaneously determining the concentrations of eight antituberculous drugs in plasma by adopting a liquid chromatography-mass spectrometry method, wherein the eight antituberculous drugs comprise rifudine, chlorphenazine, levofloxacin, clarithromycin, sulfimide, p-aminosalicylic acid, moxifloxacin and amikacin. According to the method, the characteristics of hydrophilic and hydrophobic compounds are considered, protein precipitation is carried out by utilizing ACN:MEOH:45%TCA, the extraction rate of the hydrophilic compound AMK is improved, 20% of ACN, 0.2% of FA and 1% of HFBA are used as diluents, and the retention time of the hydrophilic compound AMK is prolonged by adding the HFBA. The method is high in sensitivity, strong in specificity and wide in linear range, can be used for qualitative and quantitative analysis of to-be-detected substances with unknown concentrations in plasma of tuberculosis patients, is simple and rapid to operate, does not need an extraction and volatilization process, and can meet the characteristics of urgent clinical treatment drug monitoring tasks and high requirements on detection time. The detection system provided by the invention provides a new technical platform for tuberculosis patient treatment drug monitoring, and is easy to popularize and apply.

Description

technical field [0001] The invention belongs to the field of analytical chemistry, and relates to a method for measuring the concentration of anti-tuberculosis drugs, in particular to a method for measuring 8 kinds of anti-tuberculosis drugs in plasma: rifabutin, clofenazine, levofloxacin, clarithromycin, sulfimide, Methods for concentrations of aminosalicylic acid, moxifloxacin, and amikacin. The method is simple and rapid, and is suitable for clinical therapeutic drug monitoring. Background technique [0002] According to data records, tuberculosis is still a major infectious disease that endangers human life and health, and the prevalence of drug-resistant tuberculosis (DR-TB), especially multi-drug-resistant tuberculosis (MDR-TB), is becoming increasingly serious. According to the survey, although the standard treatment regimen consisting of the first-line anti-TB drugs isoniazid, rifampicin, ethambutol and pyrazinamide is effective in the treatment of tuberculosis, the...

AI Technical Summary

Problems solved by technology

At present, the sputum culture method commonly used in clinical tuberculosis drug resistance detection takes a long time, which often leads to a relative lag in the judgment of curative effect, while TDM is fast and has a large throughput, which is more conducive to the promotion of individualized drug administration in clinical practice.

[0005] Prior art carries out in TDM detection, at first must have the method for blood drug concentration determination, the method of TDM commonly used at present mainly contains three big classes: 1. chromatographic method: comprise spectrophotometry and high performance liquid chromatography; 2. Immunological method : including enzyme immunoassay, fluorescence immunoassay, chemiluminescence immunoassay and fluorescence polarization immunoassay (FPIA); 3. mass spectrometry: including liquid chromatography tandem mass spectrometry and gas chromatography tandem mass spectrometry; such as antibiotics - vancomycin used High-performance liquid chromatography (HPLC) and fluorescence polarization immunoassay (FPIA) were used for detection; antiepileptic drug - phenytoin was detected by ultraviolet spectrophotometry, enzyme-linked immunosorbent assay, capillary zone electrophoresis or fluorescence polarization immunoassay; however Due to the complex components in biological samples (plasma), the biological matrix often interferes with the determination of drugs; and the concentration of drugs is relatively low, and commonly used chromatography is difficult to meet the determination of low-concentration drugs

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