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A highly sensitive LC–MS–MS assay for analysis of midazolam and its major metabolite in human plasma: Applications to drug metabolism

2005; Elsevier BV; Volume: 822; Issue: 1-2 Linguagem: Inglês

10.1016/j.jchromb.2005.05.011

1873-376X

Valquíria Aparecida Polisel Jabor, Eduardo Barbosa Coelho, Neife Aparecida Guinaim dos Santos, Pierina Sueli Bonato, Vera Lúcia Lanchote,

Pharmacological Effects and Toxicity Studies

The present report describes a rapid, selective and a highly sensitive assay for midazolam (MDZ) and its major metabolite 1-hydroxymidazolam (1-OH-MDZ) in human plasma employing liquid chromatography–tandem mass spectrometry (LC–MS–MS) detection. The method involves liquid–liquid extraction sample clean-up, separation on a Purospher RP 18-e column and detection with an electrospray interface in the positive ion mode. The overall recoveries were about 100% and 80% for midazolam and 1-hydroxymidazolam, respectively. Accuracy, precision and linearity were acceptable for biological samples with quantitation limits of 0.1–100 ng mL−1 plasma for both analytes. The validated method was successfully applied to quantify plasma concentration of midazolam and 1-hydroxymidazolam in authentic samples from a healthy volunteer following a single 15 mg oral dose of midazolam (apparent total clearance: 3.47 L h−1 kg−1 and AUC0 − αIOH-MDZ/MDZ: 0.338).