Determination of perospirone by liquid chromatography/electrospray mass spectrometry: Application to a pharmacokinetic study in healthy Chinese volunteers

Perospirone is a novel atypical antipsychotic with a unique combination of 5-HT1A receptor agonism as well as 5-HT2A and D2 receptor antagonism. A simple rapid and selective LC–MS method utilizing a single quadrupole mass spectrometer was developed and validated for the determination of perospirone hydrochloride in human plasma. N-hexane was used to extract perospirone hydrochloride and amlodipine benzenesulfonate (internal standard (IS)) from an alkaline plasma sample. LC separation was performed on a XTerra ® MS C18 column (100 mm × 2.1 mm, i.d. 3.5 μm) using methanol −10 mM ammonium acetate (84:16, v/v) as a mobile phase. The quantification of target compounds was obtained by using a selected ion monitoring (SIM) at m/z 427.5 [M + H]+ for perospirone hydrochloride, and at m/z 431.4 [M + Na]+ for IS (amlodipine benzenesulfonate). Perospirone and IS eluted as sharp, symmetrical peaks with retention times of 3.11 ± 0.01 min and 4.15 ± 0.2 min, respectively. Calibration curves of perospirone hydrochloride in human plasma at concentrations ranging from 0.10 to 21.1 ng/mL exhibited excellent linearity (r2 = 0.9997). The mean absolute recovery of the drug from plasma was more than 85%. Intra- and inter-day relative standard deviations were less than 6.43% and 11.9% for perospirone hydrochloride at the range from 0.32 to 10.6 ng/mL. Stability characteristics of the drug-containing plasma were thoroughly evaluated to establish appropriate conditions to process, store and prepare for chromatographic analysis without inducing significant chemical degradation. The following pharmacokinetic parameters were elucidated after administering a single dose of 8 mg perospirone hydrochloride. The area under the plasma concentration versus time curve from time 0 to 24 h (AUC0–24) was 15.48 ± 4.23 μg/L h; peak plasma concentration (Cmax) was 2.79 ± 0.78 μg/L; time to Cmax (Tmax) was 1.79 ± 0.45 h; and elimination half-life (t1/2) 6.78 ± 1.38 h. The described assay method showed acceptable precision, accuracy, linearity, stability, and specificity and can be used for pharmacokinetic studies, therapeutic drug monitoring, and drug abuse screening.