Sensitive and Specific Lc-MS/MS Method for the Simultaneous Determination of Chlorproguanil, Dapsone, and Their Metabolites in Human Plasma

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 lL 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 lm) 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-D 3 (TMP-D 3 , 298 ->103) was monitored using multiple reaction monitoring. The lower limit of detection for CPG, CCG, DDS, and MADDS was 0.5 ng mL À1 while the limit of quantification was 2 ng mL À1 in human plasma. The extraction recovery of CPG, CCG, DDS, MADDS, and TMP-D 3 from human plasma was higher than 87%. The method may find its application in therapeutic monitoring of these compounds in biological matrix.