Method for simultaneous analysis of nine second-line anti-tuberculosis drugs using UPLC-MS/MS

Area of Science:

• Analytical Chemistry
• Pharmacology
• Clinical Chemistry

Background:

• Therapeutic drug monitoring (TDM) is crucial for optimizing anti-tuberculosis (TB) treatment, especially for slow responders and multidrug-resistant cases.
• Accurate quantification of second-line TB drugs is essential for effective patient management.

Purpose of the Study:

• To develop and validate a rapid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method.
• To simultaneously measure blood concentrations of nine key second-line anti-TB drugs.

Main Methods:

• Serum samples underwent acidified methanol extraction and neutralization.
• UPLC separation was performed using a HSS T3 column with specific mobile phases.
• Drug quantification utilized multiple reaction monitoring in positive ion mode.

Main Results:

• The method achieved rapid chromatographic separation within 3 minutes per sample.
• High precision (1.7%-7.5% within-run, 1.7%-12.4% between-run) and sensitivity (LOD 0.025-0.5 μg/mL) were demonstrated.
• The assay showed acceptable linearity and minimal ion suppression for most compounds.

Conclusions:

• The UPLC-MS/MS method is rapid, sensitive, and reproducible for quantifying nine second-line anti-TB drugs.
• This assay facilitates effective drug monitoring during anti-TB therapy.
• The method's performance is generally acceptable for clinical application.