A selective LC-MS/MS method for simultaneous quantification of Artemether, Lumefantrine and their principle metabolites in human plasma

Authors

  • Martin O. Ongas Center for Research in Therapeutic Sciences, Strathmore University, Kenya
  • Elizabeth Juma Centre for Clinical Research, Kenya Medical Research Institute, Kenya
  • Caroline G Kirimi Center for Research in Therapeutic Sciences, Strathmore University, Kenya
  • Florence Oloo Center for Research in Therapeutic Sciences, Strathmore University, Kenya
  • Gilbert Kokwaro Center for Research in Therapeutic Sciences & Institute of Healthcare Management, Strathmore University, Kenya
  • Rashid Aman Center for Research in Therapeutic Sciences, Strathmore University & African Centre for Clinical Trials (ACCT), Kenya
  • Bernhards R. Ogutu Center for Research in Therapeutic Sciences, Strathmore University & Centre for Clinical Research, Kenya Medical Research Institute, Kenya

DOI:

https://doi.org/10.18034/ra.v6i3.335

Keywords:

Artemether, Lumefantrine, Metabolites, LC-MS/MS, Pharmacokinetics, Human plasma

Abstract

We have developed and validated a sensitive, selective and reproducible reversed-phase high-performance liquid chromatography method coupled with electrospray ionization mass spectrometry (HPLC–ESI-MS/MS) for the simultaneous quantitation of artemether (ART), dihydroartemisinin (DHA), lumefantrine (LUM) and desbutyl-lumefantrine (DBL) in human plasma. Mefloquine was used as an internal standard (IS). The analytes were extracted by protein precipitation procedure and separated on a reversed-phase Zorbax SB-Ciano column with a mobile phase composed of acetonitrile and 20mM aqueous ammonium formate containing 0.5% (v/v) formic acid. Multiple reaction monitoring was performed in the positive ion mode using the transitions m/z 316.3→m/z 163.1 (ART), m/z 302.3→m/z 163.1 (DHA), m/z 530.3→m/z 512.2. (LUM), m/z 472.2→m/z 454.1 (DBL) and m/z 379.1→m/z 361.1(MQ) to quantify the drugs. Calibration curves in spiked plasma were linear (r2 ≥ 0.9992) over the range of 5–1500 ng/mL for ART/ DHA and 5–5,000 ng/mL for LUM/DBL. The lower limit of quantitation (LLOQ) was 10 ng/mL ART/ DHA and 5 ng/mL for LUM/ DBL. The mean R.S.D. values for the intra-run precision were 2.2% , 3.8%, 1.9%  and 4.7% and for the inter-run precision were 3.2%, 3.6% , 4.4%  and 3.5% for ART, DHA, LUM  and DBL, respectively. The mean percentage recovery values were 93.2%, 98.5%, 97.1% and 99.4% for ART, DHA, LUM and DBL, respectively. No matrix effect was detected for all the analytes and the IS. The validated method was successfully applied to determine the plasma concentrations of ART, DHA, LUM and DBL in pregnant and non-pregnant women volunteers in a multiple-dose pharmacokinetics study over the course of 336 hours.

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Published

2018-12-31

How to Cite

Ongas, M. O., Juma, E., Kirimi, C. G., Oloo, F., Kokwaro, G., Aman, R., & Ogutu, B. R. (2018). A selective LC-MS/MS method for simultaneous quantification of Artemether, Lumefantrine and their principle metabolites in human plasma. ABC Research Alert, 6(3), Kenya. https://doi.org/10.18034/ra.v6i3.335

Issue

Vol. 6 No. 3 (2018): September-December Issue

Section

Research Paper

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