Simultaneous determination of blonanserin and its four metabolites in human plasma using ultra-performance liquid chromatography–tandem mass spectrometry

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 939; pp. 59 - 66
• Main Authors: Zhou, Ying, Liu, Ming, Jiang, Ji, Wang, Hongyun, Hu, Pei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.11.2013
• Subjects: Blonanserin; Chromatography; Chromatography, High Pressure Liquid - methods; Determination; Drug Stability; Extraction; Formates; formic acid; Human; Human plasma; Humans; Ionization; Least-Squares Analysis; Liquid chromatography; Mass spectrometry; Metabolite; Metabolites; monitoring; pharmacokinetics; Piperazines - blood; Piperazines - chemistry; Piperazines - pharmacokinetics; Piperidines - blood; Piperidines - chemistry; Piperidines - pharmacokinetics; rapid methods; Reproducibility of Results; Sensitivity and Specificity; Solid Phase Extraction; tandem mass spectrometry; Tandem Mass Spectrometry - methods; ultra-performance liquid chromatography; UPLC–MS/MS; Human plasma; Determination; Blonanserin; Metabolite; UPLC–MS/MS
• ISSN: 1570-0232; 1873-376X; 1873-376X
• DOI: 10.1016/j.jchromb.2013.09.007

•The method has been developed and validated for the simultaneous determination of blonanserin and its four metabolites in human plasma for the first time.•The total run time was much faster and the plasma volume required for sample preparation was much smaller compared to previous literatures.•The method was fully validated and applied successfully in a clinical study. A sensitive and rapid method based on ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC–MS/MS) was developed and validated for the simultaneous determination of blonanserin, its major active metabolite (N-deethyl form) and other three metabolites (N-oxide form, Ethylenediamine form and Carboxylate form) in human plasma. Plasma samples were pre-purified by solid-phase extraction (SPE) and analyzed using a gradient chromatographic separation over an Acquity UPLC CSH C18 column. The mobile phase consisted of acetonitrile–water containing 5mM ammonium formate and 0.1% formic acid at a flow rate of 0.5mL/min. Positive electrospray ionization was employed as the ionization source in the multiple reaction monitoring (MRM) mode. The analysis time was about 3.5min. The method was fully validated over the concentration range of 0.01–1ng/mL for all analytes. The lower limit of quantification (LLOQ) was 0.01ng/mL. Inter- and intra-batch precision was less than 15% and the accuracy was within 85–115%. The mean extraction recoveries of all analytes at two concentration levels were consistent. Selectivity, matrix effect and stability were also validated. The method was applied to the pharmacokinetic study of blonanserin in Chinese healthy subjects.