title: A sensitive and selective liquid chromatographic/electrospray ionization tandem mass spectrometric assay for the simultaneous quantification of alpha-,beta-arteether and its metabolite dihydroartemisinin in plasma, useful for pharmacokinetic studies.
abstract: A sensitive, selective, specific and rapid liquid chromatographic/electrospray ionization tandem mass spectrometric assay method was developed and validated for the simultaneous quantitation of alpha-,beta-arteether (alpha-,beta-AE) and its metabolite alpha-dihydroartemisinin (DHA) in monkey plasma using the propyl ether analogue of beta-arteether (PE) as an internal standard. The method involves a simple two-step liquid-liquid extraction with hexane. The analytes were chromatographed on a C(18) reversed-phase chromatographic column by isocratic elution with methanol-ammonium acetate buffer (pH 4) (92 : 8, v/v) and analysed by mass spectrometry in the multiple reaction monitoring mode. The chromatographic run time was 7 min and the weighted (1/x(2)) calibration curves were linear over the range 0.78-200 ng ml(-1). The method was validated in terms of accuracy, precision, absolute recovery, freeze-thaw stability, bench-top stability and re-injection reproducibility. The limit of detection and lower limit of quantification in monkey plasma were 0.39 and 0.78 ng ml(-1) respectively for all the analytes. The intra- and inter-batch precision and accuracy were found to be well within acceptable limits (<15%). All three analytes were stable even after three freeze-thaw cycles (deviation < 15%). The average absolute recoveries of alpha-,beta-AE, DHA and PE, used as an internal standard, from spiked plasma samples were 85.85 +/- 6.56, 70.10 +/- 7.06, 54.37 +/- 3.39 and 93.90 +/- 6.9%, respectively. The assay method described here could be applied to study the pharmacokinetics of alpha-,beta-AE and DHA in rhesus monkeys.
authors.affiliation: Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow 226001, India.
authors.forename: S
authors.initials: S
authors.lastname: Sabarinath
authors.forename: M
authors.initials: M
authors.lastname: Rajanikanth
authors.forename: K P
authors.initials: KP
authors.lastname: Madhusudanan
authors.forename: R C
authors.initials: RC
authors.lastname: Gupta
mesh_terms: D000962:Antimalarials / Q000032:analysis* / Q000493:pharmacokinetics*; D037621:Artemisinins / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D012680:Sensitivity and Specificity; D012717:Sesquiterpenes / Q000032:analysis* / Q000493:pharmacokinetics*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C039060:artenimol; C055141:artemotil