ABSTRACT
OBJECTIVE: To establish an LC-MS/MS method for simultaneous determination of blonanserin and its metabolite blonanserin C in the plasma of healthy volunteers. METHODS: After adding saturated aqueous solution of sodium bicarbonate as the basification reagent, blonanserin and blonanserin C were extracted from plasma by ethyl acetate-dichloromethane (4;1). Then blonanserin and blonanserin C were determined by LC-MS/MS using blonanserin B and blonanserin D as internal standards respectively. Separation was carried on an Agilent Eclipse plus C18 column(4.6 mm×150 mm, 5 μm)with a mobie phase of acetonitrile-0.005 mol·L-1 ammonium formate aqueous solution containing 0.1% formic acid (87;13) at the flow rate of 0.5 mL·min-1. The column temperature was set at 40°C. ESI source was applied and operated in positive ion mode. Quantitative determination was performed using selective reaction monitoring (SRM) at m/z 368.2→297.2 for blonanserin, m/z 396.3→297.2 for blonanserin B, m/z 340.2→297.1 for blonanserin C and m/z 356.2→313.3 for blonanserin D. RESULTS: Blonanserin and blonanserin C showed good linearity in the range of 10-2000 ng·L-1(r2=0.997). The extraction recoveries for blonanserin and blonanserin C were more than 93.5% and 74.5% respectively, while the intra-day and inter-day RSDs were lower than 9.0% and 16.4% respectively. CONCLUSION: The method is simple, rapid, accurate and sensitivie for simultaneous determination of blonanserin and blonanserin C in human plasma, which can be applied to the clinical pharmacokinetic study and therapeutic drug monitoring of blonanserin.