Simple and Sensitive Analysis of Blonanserin and Blonanserin C in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry and Its Application

Xingjiang Hu,Huili Zhou,Jianzhong ShenTu,Meixiang Zhu,Jian Liu,You Zhai,Guolan Wu,Yunliang Zheng,Lihua Wu

doi:10.1155/2014/629343

Abstract

A highly sensitive, simple, and rapid liquid chromatography tandem mass spectrometry method to simultaneously determine blonanserin and blonanserin C in human plasma with AD-5332 as internal standard (IS) was established. A simple direct protein precipitation method was used for the sample pretreatment, and chromatographic separation was performed on a Waters XBridge C8 (4.6 × 150 mm, 3.5 μm) column. The mobile phase consists of a mixture of 10 mM ammonium formate and 0.1% formic acid in water (A) and 0.1% formic acid in methanol (B). To quantify blonanserin, blonanserin C, and IS, multiple reaction monitoring (MRM) was performed in positive ESI mode. The calibration curve was linear in the concentration range of 0.012–5.78 ng·mL−1 for blonanserin and 0.023–11.57 ng·mL−1 for blonanserin C (r 2 > 0.9990). The intra- and interday precision of three quality control (QC) levels in plasma were less than 7.5%. Finally, the current simple, sensitive, and accurate LC-MS/MS method was successfully applied to investigate the pharmacokinetics of blonanserin and blonanserin C in healthy Chinese volunteers.

Highlights

Blonanserin (AD-5423) is a novel oral atypical antipsychotic agent with relatively selective potent activity of blocking dopamine D2 and serotonin 5-HT2A receptors, which is expected to have lower incidence of adverse events than other antipsychotics [1,2,3]
Mass spectrometer parameters were derived from analyte infusion experiments using a syringe pump
electrospray ionization (ESI) source with positive or negative ionization has been tested for the determination, and the results revealed that blonanserin, blonanserin C, and internal standard (IS) were more sensitive in positive ionization mode

Summary

Introduction

Blonanserin (AD-5423) is a novel oral atypical antipsychotic agent with relatively selective potent activity of blocking dopamine D2 and serotonin 5-HT2A receptors, which is expected to have lower incidence of adverse events than other antipsychotics [1,2,3]. High-performance liquid chromatography (HPLC) with fluorescence detection (HPLC-FLD) [9], GC-MS [13], HPLCMS/MS [14, 15], and UPLC-MS/MS [16, 17] have been reported for the determination of blonanserin in human plasma. They all need a complicated and expensive sample pretreatment method, either solid-phase extraction (SPE) or liquid-liquid extraction (LLE), for the purifying of plasma samples, so as to get a low limit of quantification (LOQ). It has been successfully applied to a pharmacokinetic study in healthy Chinese volunteers

Experimental

Results and Discussion

Method Validation

Conclusion