Simple and sensitive method for analysis of 14 anti-tuberculosis drugs using LC/MS/MS in human plasma.Rapid Commun Mass Spectrom 2019RC
The monitoring of the plasma concentration and dose adjustment of anti-tuberculosis (TB) drugs are beneficial for improving responses to drug treatment and avoiding drug adverse reactions. A simple and sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed to measure the plasma concentrations of 14 anti-TB drugs: ethambutol, isoniazid, pyrazinamide, levofloxacin, gatifloxacin, moxifloxacin, prothionamide, linezolid, rifampin, rifapentine, rifabutin, cycloserine, p-aminosalicylic acid (PAS) and clofazimine.
Human plasma was precipitated by acetonitrile and was subsequently separated by an AQ-C18 column with a gradient elution. Drug concentrations were determined using multiple reaction monitoring (MRM) in positive ion ESI mode. According to pharmacokinetic data of patients, the peak concentration ranges and timing of blood collection were determined.
Intra- and inter-day precision was less than 14.8%. Linearity, accuracy, extraction recovery and matrix effect were acceptable for each drug. Stability of the method satisfied different storage conditions.
The method applied the sensitive and reproducible determination of 14 frequently-used anti-TB drugs, which already showed benefit for some TB patients.