Abstract
A simple, rapid, and sensitive liquid chromatography (LC)/mass spectrometry (MS) method was established and validated for simultaneous quantitation of pyrazinamide, isoniazid, rifampicin, and ethambutol in human blood sample. Samples were pretreated by a single-step precipitation with acetonitrile. Chromatographic separation was achieved on XSelecT HSS T3 column by gradient elution with a total run time of 5.0 min. MS detection was performed by a triple quadrupole tandem mass spectrometer in the multiple reaction monitoring mode with a positive electrospray ionization source. Isotope-labeled internal standard, especially rifampicin-D8, was applied to adjust for the loss during sample treatment. The established LC-MS/MS method showed a wide analytical range (pyrazinamide: 1.02∼60.0 μg/mL, isoniazid: 0.152∼10.0 μg/mL, rifampicin: 0.500∼30.0 μg/mL, and ethambutol: 0.0998∼5.99 μg/mL) and a good linearity (r > 0.99 for the four analytes) with acceptable accuracy and precision (90.15%∼104.62% and 94.00%∼104.02% for intra- and interaccuracy, respectively; RSD%: <12.46% and <6.43% for intra- and interprecision, respectively). It also showed excellent recoveries (79.24%∼94.16% for all analytes) and absence of significant matrix effect. This method was successfully applied to the quantification of four first-line antituberculosis (anti-TB) drugs, suggesting its suitability for therapeutic drug monitoring in the clinical practices.
Highlights
Tuberculosis (TB) is an ancient disease, but it is still one of the top ten causes of death, which kills 1.5 million people every year all over the world [1, 2]
No interfering peaks at specific retention times of analytes of interest were observed in Double blank solution (DB) and B, showing an excellent selectivity
Regression equations and correlation coefficients of each analyte were calculated by integrating the results from three runs
Summary
Tuberculosis (TB) is an ancient disease, but it is still one of the top ten causes of death, which kills 1.5 million people every year all over the world [1, 2]. A long-term treatment with multiple drugs is necessary for TB patients [3], which was proposed as follows [4]: an intensive phase with four first-line antituberculosis drugs (pyrazinamide (PZA), isoniazid (INH), rifampicin (RFP), and ethambutol (EMB)) for the first two months, followed by a continuation phase with isoniazid and rifampicin for the four months. This regimen is highly effective for most drugsusceptible TB patients, some patients do not respond adequately and even suffer from treatment failure and drug resistance [5]. Some adverse drug effects, such as hepatic dysfunction and thrombocytopenia, will develop more frequently with increasing serum drug levels [8]. erapeutic drug
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
