An LC–MS–MS method for the determination of cyclizine in human serum

Cyclizine is a piperazine derivative with anti-emetic activity that is useful in the prevention and treatment of nausea and vomiting associated with motion sickness. A liquid chromatography–tandem mass spectrometry (LC–MS–MS) method is presented for the quantitation of cyclizine in serum. Sample pretreatment involved liquid–liquid extraction of 200 μl of serum with dichloromethane after the addition of 100 μl each of ammonium hydroxide and internal standard solutions. The extracts were analyzed by HPLC on a Luna® C18 reversed-phase column and an ion-trap mass spectrometer with an electrospray interface. A limit of detection of 1 ng/ml was determined which allowed for the reliable measurement of cyclizine in the serum of human subjects. The method was found to be linear over the calibration range of 2.5–100 ng/ml. The applicability of this method was demonstrated by the analysis of serum obtained from a human volunteer following administration of a single 50 mg cyclizine hydrochloride tablet. The reported method was observed to have the necessary sensitivity, selectivity, precision and accuracy for monitoring cyclizine concentrations in human subjects following oral administration.