title: Simultaneous determination of blonanserin and its metabolite in human plasma and urine by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study.
abstract: Blonanserin is a novel atypical antipsychotic with highly selective receptor antagonist activity to dopamine D₂ and 5-HT(2A). N-desethyl blonanserin (blonanserin C) is its major active metabolite in human plasma. Herein we report a new highly sensitive, selective, and rapid liquid chromatography-tandem mass spectrometry method to determine blonanserin and blonanserin C simultaneously in human plasma and urine, with N-desethyl-chlor-blonanserin (blonanserin D) as internal standard (IS). Blonanserin and blonanserin C were extracted from aliquots of plasma and urine with ethyl acetate and dichloromethane (4:1) as the solvent and chromatographic separation was performed using an Agilent Eclipse Plus C₁₈ column. The mobile phase was composed of: acetonitrile and ammonium formate-formic acid buffer containing 5mM ammonium formate and 0.1% formic acid (87:13, v/v). To quantify blonanserin, blonanserin C, and blonanserin D, respectively, multiple reaction monitoring (MRM) transition of m/z 368.2→297.2, m/z 340.2→297.1, and m/z 356.2→313.3 was performed in positive mode. The analysis time was about 5.5 min. The calibration curve was linear in the concentration range of 0.01-2 ng/ml. The lower limit of quantification reached 0.01 ng/ml. The intra and inter-day precision and relative errors were less than 8.0% and 6.6% for three QC levels in plasma and urine. The current LC-MS/MS method was validated as simple, sensitive, and accurate and has been successfully applied to investigate the pharmacokinetics of blonanserin and blonanserin C in humans.
authors: Department of Pharmacy, Guangzhou Brain Hospital, Guangzhou Medical University, 36 MingXin Road, Guangzhou 510370, China. wen.yuguan@yahoo.cn
authors: Yu-Guan
authors: YG
authors: Wen
authors: Xiao-Jia
authors: XJ
authors: Ni
authors: Ming
authors: M
authors: Zhang
authors: Xia
authors: X
authors: Liu
authors: De-Wei
authors: DW
authors: Shang
mesh_terms: D000293:Adolescent; D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine*; D010880:Piperidines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D010879:Piperazines; D010880:Piperidines; C079310:blonanserin