Development and validation of hplc method for simultaneous determination of haloperidol and reduced haloperidol in plasma: application in pharmacokinetic study

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dc.contributor.authorAsualingam, Theepa
dc.date.accessioned2015-07-30T03:04:49Z
dc.date.available2015-07-30T03:04:49Z
dc.date.issued2007
dc.description.abstractHaloperidol is a typical antipsychotic drug that chemically belongs to butyrophenone group. A sensitive and selective reversed-phase HPLC method with ultraviolet detection was developed for the simultaneous determination of haloperidol and reduced haloperidol in plasma. Drugs were detected at 230 nm. The chromatographic separation was performed on an lnertsil C8-3 (150 x 4.6mm, 5 llm) HPLC column. Mobile phase composed. of 50 mM phosphate buffer pH 5.0 and methanol (51 :49, v/v) and eluted at 1.0 mllmin. A simple liquid-liquid extraction was carried-out using pyrimethamine as an internal standard. The mean extraction recovery for haloperidol, reduced haloperidol and pyrimethamine were 82.4, 82.1 and 82.0% respectively. The method showed good selectivity with respect to commonly administered psychotropic drugs. Calibration curve was linear over the concentration range 1 - 60 ng/ml with the correlation coefficient (r) > 0.999. The within-day and day-to -day assay precision was less than 5%. Limit of detection and lower limit of quantification were 0.5 ng/ml and 1 ng/ml respectively for haloperidol and reduced haloperidol. Stock standard of haloperidol and reduced haloperidol in methanol were stable up to three months at -20°C. Plasma samples spiked with haloperidol and reduced haloperidol was stable up to 6 months at -20°C and -85°C. The method was successfully applied to pharmacokinetic study of haloperidol in rats following oral dose of haloperidol (2.5 mg/kg). The mean t112. Cmax. tmax. AUC (O-oo)• CL and Vd were 6.2 ± 2.6 h, 24.9 ± 7.2 ng/ml, 2.0 ± 1.9 h, 214.1 ± 76.0 ng.h/ml, 213.0 ± 61.9 ml/min/kg and 110.3 ± 46.3 1/kg respectively. The analytical method for haloperidol and reduced haloperidol assay is found to be suitable for pharmacokinetic studies.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/942
dc.language.isoenen_US
dc.subjectSimultaneous determinantionen_US
dc.subjectReduced haloperidolen_US
dc.subjectPharmacokineticen_US
dc.titleDevelopment and validation of hplc method for simultaneous determination of haloperidol and reduced haloperidol in plasma: application in pharmacokinetic studyen_US
dc.typeThesisen_US
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