Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, 31270-901, Belo Horizonte, MG, Brazil.
J Pharm Biomed Anal. 2011 Jan 5;54(1):114-20. doi: 10.1016/j.jpba.2010.07.027. Epub 2010 Aug 17.
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.
建立并验证了一种液相色谱-电喷雾串联质谱（HPLC-ESI-MS/MS）法，用于同时定量测定人血浆中的青蒿素和咯萘啶。青蒿琥酯用作内标（IS）。通过蛋白沉淀法提取分析物，在反相 Zorbax SB-Ciano 柱上分离，流动相由甲醇和 10mM 含 0.2%（v/v）乙酸和 0.1%（v/v）甲酸的乙酸铵组成。采用多重反应监测，分别用质荷比 m/z 316→m/z 267、m/z 530→m/z 348 和 m/z 402→m/z 267 定量测定青蒿素、咯萘啶和青蒿琥酯。青蒿素的校准曲线范围为 10-1000ng/mL，咯萘啶的校准曲线范围为 10-18000ng/mL。两种药物的定量下限均为 10ng/mL。青蒿素和咯萘啶的内、日间精密度的 R.S.D.值分别为 2.6%和 3.0%、3.6%和 4.6%。青蒿素和咯萘啶的准确度均值分别为 102.0%和 101.2%。样品中未检测到基质效应。该验证方法成功应用于 11 天的单剂量药代动力学研究中，测定健康志愿者血浆中的青蒿素和咯萘啶浓度。
