Simultaneous Determination of Atenolol and Chlorthalidone by LC–MS–MS in Human Plasma

Abstract

A simple, sensitive, selective and rapid liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous separation and quantitation of atenolol and chlorthalidone in human plasma using metoprolol and hydrochlorothiazide as internal standard. Following solid phase extraction, the analytes were separated by an isocratic mobile phase on a reversed-phase C18 column and analyzed by MS in the multiple reaction-monitoring mode (atenolol in positive and chlorthalidone in the negative ion mode). The limit of quantitation for this method was 10 and 15 ng mL−1 and the linear dynamic range was generally 10–2,050 ng mL−1 and 15–3,035 ng mL−1 for atenolol and chlorthalidone, respectively.