A sensitive and selective liquid chromatographic/electrospray ionization tandem mass spectrometric assay for the simultaneous quantification of α-,β-arteether and its metabolite dihydroartemisinin in plasma, useful for pharmacokinetic studies

✍ Scribed by S. Sabarinath; M. Rajanikanth; K. P. Madhusudanan; R. C. Gupta

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 194 KB
• Volume: 38
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/jms.487

✦ Synopsis

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 α‐,β‐arteether (α‐,β‐AE) and its metabolite α‐dihydroartemisinin (DHA) in monkey plasma using the propyl ether analogue of β‐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 α‐,β‐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 α‐,β‐AE and DHA in rhesus monkeys. Copyright © 2003 John Wiley & Sons, Ltd.