[Determination of risperidone in human plasma by liquid chromatography-tandem mass spectrometry].
OBJECTIVE
To develop and validate a liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for the determination of risperidone in human plasma.


METHODS
Risperidone and the internal standard, diphenhydramine, were isolated from plasma by liquid-liquid extraction with etherdichloromethane (3:2, v/v) , then chromatographed on a Zorbax Extend-C18 column (150 mm x 4.6 mm ID, 5 microm) using a mobile phase consisted of acetonitrile-water-formic acid (40:60: 0.5, v/v), at a flow rate of 0.7 mL x min(-1). A Finnigan TSQ tandem mass spectrometer equipped with atmospheric pressure chemical ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor product ion combinations of m/z 411-->191 and m/z 256-->167 were used to quantify risperidone and diphenhydramine (IS) , respectively.


RESULTS
The linear concentration range of the calibration curve for risperidone was 0.025 - 50 microg L(-1). The lower limit of quantification was 0.025 microg x L(-1). The intra- and inter-day relative standard deviation (RSD) across three validation running over the entire concentration range was less than 7.1%. The accuracy was within +/- 3.8%. Each sample was chromatographed within 2.7 min.


CONCLUSIONS
The method was proved to be rapid, sensitive and suitable for pharmacokinetic investigations of risperidone.
Duan
Xiao-tao
XT
Center for Drug Metabolism Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Chen
Xiao-yan
XY
Zhang
Yi-fan
YF
Zhong
Da-fang
DF
D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D004155:Diphenhydramine / Q000097:blood / Q000592:standards; D006801:Humans; D008297:Male; D012015:Reference Standards; D015203:Reproducibility of Results; D018967:Risperidone / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
D014150:Antipsychotic Agents; D004155:Diphenhydramine; D018967:Risperidone