title: Liquid chromatography/tandem mass spectrometry method for the simultaneous determination of olanzapine, risperidone, 9-hydroxyrisperidone, clozapine, haloperidol and ziprasidone in rat plasma.
abstract: A simple, sensitive and rapid liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method was developed and validated for simultaneous quantification of olanzapine, clozapine, ziprasidone, haloperidol, risperidone, and its active metabolite 9-hydroxyrisperidone, in rat plasma using midazolam as internal standard (IS). The analytes were extracted from rat plasma using a single step liquid-liquid extraction technique. The compounds were separated on a Waters Atlantis dC-18 (30 mm x 2.1 mm i.d., 3 microm) column using a mobile phase of acetonitrile/5 mM ammonium formate (pH 6.1 adjusted with formic acid) with gradient elution. All of the analytes were detected in positive ion mode using multiple reaction monitoring (MRM). The method was validated and the specificity, linearity, lower limit of quantitation (LLOQ), precision, accuracy, recoveries and stability were determined. LLOQ was 0.1 ng/mL and correlation coefficient (R(2)) values for the linear range of 0.1-100 ng/mL were 0.997 or greater for all the analytes. The intra-day and inter-day precision and accuracy were better than 8.05%. The relative and absolute recovery was above 77% and matrix effects were low for all the analytes except for ziprasidone. This validated method has been successfully used to quantify the plasma concentration of the analytes after chronic treatment with antipsychotic drugs.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602-2352, USA.
authors.forename: Guodong
authors.initials: G
authors.lastname: Zhang
authors.forename: Alvin V
authors.initials: AV
authors.lastname: Terry
authors.forename: Michael G
authors.initials: MG
authors.lastname: Bartlett
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood*; D001774:Blood Chemical Analysis / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D045424:Complex Mixtures / Q000032:analysis; D008297:Male; D008832:Microchemistry / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D014150:Antipsychotic Agents; D045424:Complex Mixtures