Liquid Chromatography-Tandem Mass Spectrometry Methods for Determination of Delamanid in Mouse Plasma and Lung

Abstract

Sensitive and selective liquid chromatography-tandem mass spectrometry methods have been developed and validated for the determination of delamanid in mouse plasma and lung. Sample preparation involved liquid-liquid extraction with diethyl ether for plasma, or protein precipitation followed by liquid-liquid extraction with tert-butyl methyl ether for lung homogenate. Chromatographic separation was performed on a reversed phase column with a linear gradient elution using purified water-formic acid (1000:2, v/v) and methanol-formic acid (1000:2, v/v) at a flow rate of 0.2 mL/min. Detection was performed on a triple-quadrupole tandem mass spectrometer using positive ion electrospray ionization in the selected reaction monitoring mode. The analytical methods were successfully validated for selectivity, calibration curve, accuracy, precision, extraction recovery, and stability over a range of 6 - 1000 ng/mL for plasma and 10 - 1000 ng/mL for lung homogenate. The validated methods were successfully applied for evaluation of pharmacokinetics of delamanid in male mice.