Abstract
A sensitive, specific, and rapid liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for the determination of dapsone, chlorproguanil, and their metabolites was developed and validated over a concentration range of 2–2000 ng/mL using 200 µL of plasma. After a simple solvent precipitation procedure, the supernatant was analyzed directly by HPLC-MS/MS method using an XTerra RP18 (2.1 mm × 100 mm, 5.0 µm) column with mobile phase consisting of acetonitrile-0.1% formic acid in water (75:25, v/v, pH 3.0) in an isocratic mode at a flow rate of 0.3 mL/min. Mass detection was performed using a triple quadrupole mass spectrometer operating in positive electrospray ionization mode. The elution of chlorproguanil (CPG, 288 ->204), chlorcycloguanil (CCG, 286 ->229), dapsone (DDS, 249 ->156), monoacetyldapsone (MADDS, 291 ->156), and trimipramine-D3 (TMP-D3, 298 ->103) was monitored using multiple reaction monitoring. The lower limit of detection for CPG, CCG, DDS, and MADDS was 0.5 ng mL−1 while the limit of quantification was 2 ng mL−1 in human plasma. The extraction recovery of CPG, CCG, DDS, MADDS, and TMP-D3 from human plasma was higher than 87%. The method may find its application in therapeutic monitoring of these compounds in biological matrix.
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