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.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the pharmacokinetics of nalmefene after intravenous administration at a single or multiple doses in Chinese healthy volunteers.</p><p><b>METHODS</b>This open, randomized clinical trial involved 12 healthy volunteers, who received a single-dose (2 mg) nalmefene injection. Before and at different time points after the injection, blood sample were obtained from the subjects. After the single intravenous dose trial, 8 healthy volunteers received intravenous nalmefene at 2 mg once daily for 6 consecutive days, and the plasma drug concentrations were determined on the morning of days 4, 5 and 6 using liquid chromatography/tandem mass spectrometry and the pharmacokinetic parameters were calculated using PKS program.</p><p><b>RESULTS</b>The main pharmacokinetic parameters of nalmefene (Cmax, Tmax, T1/2, AUC0-48, and AUC0-infinity) after the single intravenous dose were 7.34-/+1.56 microg/L, 0.08 h, 12.01-/+2.20 h, 30.29-/+9.84 microg.L(-1).h, and 32.23-/+9.94 microg.L(-1).h, respectively; the parameters after multiple doses were 8.04-/+1.09 microg/L, 0.08 h, 12.43-/+1.44 h, 33.64-/+9.15 microg.L(-1).h and 35.98-/+9.23 microg.L(-1).h, respectively. The steady-state pharmacokinetic parameters including the degree of fluctuation (DF), AUCss and Cav were 4.69-/+1.29, 19.64-/+6.20 microg.L(-1).h and 1.64-/+0.52 microg/L, respectively.</p><p><b>CONCLUSION</b>Nalmefene showed similar pharmacokinetics in Chinese healthy volunteers with those in the foreign testees, and can be safely administered in healthy volunteers without producing unmanageable pain.</p>