Neal J M, Howald W N, Kunze K L, Lawrence R F, Trager W F
Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle 98195.
J Chromatogr B Biomed Appl. 1994 Nov 18;661(2):263-9. doi: 10.1016/0378-4347(94)00371-8.
An electron-capture negative-ion chemical ionization gas chromatographic-mass spectrometric assay for mefloquine, an antimalarial drug used in the treatment of drug-resistant Plasmodium falciparum malaria, is described. The method, developed in support of bioavailability studies involving the co-administration of different tableted formulations of the drug and an aqueous solution of its 13C3-labeled analog, enables quantification of both dosage forms. Quantitative analysis of extracted plasma samples was performed on the O-tert.-butyldimethylsilyl (t-BDMS) derivative of the drug by selected-ion monitoring, using a VG Trio 2000 quadrupole mass spectrometer and monitoring the [M-t-BDMSOH]-. ions of the analytes. The method, incorporating [2H6]mefloquine as an internal standard, demonstrated good accuracy and precision over the 1-200 ng ml-1 range, with correlation coefficients greater than 0.990 for all standard curves and a detection level of 50 fg on-column. Replicate analysis of plasma samples over a 90-day period exhibited a mean intra-day and inter-day variation of less than 4.5% and 5.5%, respectively. The high stability and sensitivity of the assay, combined with the inherent selectivity of mass spectrometric detection, make the method well-suited for such studies.
本文描述了一种用于测定甲氟喹的电子捕获负离子化学电离气相色谱 - 质谱分析法，甲氟喹是一种用于治疗耐药性恶性疟原虫疟疾的抗疟药物。该方法是为支持生物利用度研究而开发的，该研究涉及同时给予该药物的不同片剂剂型及其13C3标记类似物的水溶液，能够对两种剂型进行定量分析。通过选择离子监测，使用VG Trio 2000四极杆质谱仪并监测分析物的[M - t - BDMSOH]-离子，对药物的O - 叔丁基二甲基甲硅烷基（t - BDMS）衍生物的提取血浆样品进行定量分析。该方法以[2H6]甲氟喹作为内标，在1 - 200 ng ml-1范围内显示出良好的准确性和精密度，所有标准曲线的相关系数均大于0.990，柱上检测限为50 fg。在90天内对血浆样品进行重复分析，日间和日内平均变异分别小于4.5%和5.5%。该分析方法的高稳定性和灵敏度，结合质谱检测固有的选择性，使其非常适合此类研究。
