Determination of fluspirilene in human plasma by liquid chromatography tandem mass spectrometry with electrospray ionisation

An ultra-sensitive method for the determination of fluspirilene in plasma w as established, using high-performance liquid chromatographic separation wi th tandem mass spectrometric detection. The samples were extracted with hex ane/isoamyl alcohol, separated on a Phenomenex Luna C-18 5 mu 150 x 2.1 mm column with a mobile phase consisting of methanol-water-acetic acid (600:40 0:1) at a flow-rate of 0.3 ml/min. Detection was achieved by a Finnigan Mat t mass spectrometer (LCQ) at unit resolution in full scan mode scanning the product ion spectrum from m/z 130-500 and monitoring the transition of the protonated molecular ion at m/z 476.2, to the sum of the largest product i ons m/z 371, 342 and 274 (MS-MS). Electrospray ionisation was used for ion production. The mean recovery for fluspirilene was 90% with a lower limit o f quantification of 21.50 pg/ml using 1 ml plasma for extraction. This is t he first chromatographic method described for the determination of fluspiri lene in plasma that is accurate and sensitive enough to be used in pharmaco kinetic studies. (C) 1998 Elsevier Science B.V. All rights reserved.