Quantitation of Plasma Bedaquiline Concentrations in Indian MDR-TB Patients Using Liquid Chromatography-Tandem Mass Spectrometry.

Bedaquiline (BDQ) is a diarylquinoline used for the treatment of multidrug-resistant tuberculosis (MDR-TB) with a mechanism of action that inhibits the mycobacterial adenosine triphosphate synthase. There is a limited literature on the pharmacokinetics (PK) of BDQ in MDR-TB patients globally and even less from India. We aimed to develop a rapid, selective, sensitive, and robust high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to evaluate the PK of BDQ from the plasma of people with MDR-TB. The analyte was extracted from plasma by protein precipitation. The separation was achieved on a reverse phase C18 column with a mixture of aqueous and organic mobile phase in gradient mode at a flow rate of 0.3 mL/min and detected on a triple quadrupole mass spectrometer. Linearity was obtained between 0.0313 to 4.0 mg/L, and the method was validated following bioanalytical method validation guidelines. BDQ concentrations were determined from plasma samples, and intensive PK testing was performed in samples from 23 patients. The median Cmax attained was 1.59 mg/L with a Tmax around 6 h for most of our patients. This method was successfully developed and validated for a pilot PK study in Indian MDR-TB patients.