Liquid chromatography-tandem mass spectrometry for the simultaneous quantitation of artemether and lumefantrine in human plasma: application for a pharmacokinetic study.
A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the simultaneous quantitation of artemether and lumefantrine in human plasma was developed and validated. Artesunate was used as an internal standard (IS). The analytes were extracted by a protein precipitation procedure and separated on a reversed-phase Zorbax SB-Ciano column with a mobile phase composed of methanol and 10mM aqueous ammonium acetate containing 0.2% (v/v) acetic acid and 0.1% (v/v) formic acid. Multiple reaction monitoring was performed using the transitions m/z 316 → m/z 267, m/z 530 → m/z 348 and m/z 402 → m/z 267 to quantify artemether, lumefantrine and artesunate, respectively. Calibration curves were constructed over the range of 10-1000 ng/mL for artemether and 10-18,000 ng/mL for lumefantrine. The lower limit of quantitation was 10 ng/mL for both drugs. The mean R.S.D. values for the intra-run precision were 2.6% and 3.0% and for the inter-run precision were 3.6% and 4.6% for artemether and lumefantrine, respectively. The mean accuracy values were 102.0% and 101.2% for artemether and lumefantrine, respectively. No matrix effect was detected in the samples. The validated method was successfully applied to determine the plasma concentrations of artemether and lumefantrine in healthy volunteers, in a one-dose pharmacokinetic study, over the course of 11 days.
César
Isabela Costa
IC
Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil. isaccesar@bol.com.br
Ribeiro
José Antônio de Aquino
JA
Teixeira
Leonardo de Souza
Lde S
Bellorio
Karini Bruno
KB
de Abreu
Fernanda Crunivel
FC
Moreira
Josianny Mesquita
JM
Chellini
Paula Rocha
PR
Pianetti
Gerson Antônio
GA
D000085:Acetates / Q000737:chemistry; D019342:Acetic Acid / Q000737:chemistry; D000962:Antimalarials / Q000032:analysis* / Q000493:pharmacokinetics; D000077549:Artemether; D037621:Artemisinins / Q000032:analysis* / Q000493:pharmacokinetics; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004983:Ethanolamines / Q000032:analysis* / Q000493:pharmacokinetics; D005449:Fluorenes / Q000032:analysis* / Q000493:pharmacokinetics; D005561:Formates / Q000737:chemistry; D006801:Humans; D000078102:Lumefantrine; D000432:Methanol / Q000737:chemistry; D008956:Models, Chemical; D011786:Quality Control; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000085:Acetates; D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D005561:Formates; C030544:formic acid; D000077549:Artemether; D000078102:Lumefantrine; D019342:Acetic Acid; C018824:ammonium acetate; D000432:Methanol