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-HT(1A) receptor agonism as well as 5-HT(2A) and D(2) 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 C(18) column (100mmx2.1mm, i.d. 3.5microm) using methanol -10mM 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+/-0.01min and 4.15+/-0.2min, respectively. Calibration curves of perospirone hydrochloride in human plasma at concentrations ranging from 0.10 to 21.1ng/mL exhibited excellent linearity (r(2)=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 10.6ng/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 8mg perospirone hydrochloride. The area under the plasma concentration versus time curve from time 0 to 24h (AUC(0-24)) was 15.48+/-4.23microg/Lh; peak plasma concentration (C(max)) was 2.79+/-0.78microg/L; time to C(max) (T(max)) was 1.79+/-0.45h; and elimination half-life (t(1/2)) 6.78+/-1.38h. 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.
Ma
Ning
N
Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, PR China.
Liu
Wen-Ying
WY
Li
Huan-De
HD
Zhu
Yun-Gui
YG
Zhang
Bi-Kui
BK
Wang
Feng
F
Zhu
Rong-Hua
RH
Xiang
Da-Xiong
DX
D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D044466:Asian People; D002681:China; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D007211:Indoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D054833:Isoindoles; D008297:Male; D015394:Molecular Structure; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013844:Thiazoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
D014150:Antipsychotic Agents; D007211:Indoles; D054833:Isoindoles; D013844:Thiazoles; C065533:perospirone