de Santana Fernando José Malagueño, Cesarino Evandro José, Bonato Pierina Sueli
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café SN, CEP 14040-903, Ribeirão Preto, SP, Brazil.
J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Oct 5;809(2):351-6. doi: 10.1016/j.jchromb.2004.07.012.
A simple, rapid and sensitive high-performance liquid chromatography (HPLC) method was developed for the enantioselective analysis of the new antidepressant drug mirtazapine in human plasma. The procedure involved liquid-liquid extraction using toluene, followed by liquid chromatography coupled to UV detection at 292 nm. The chromatographic separation of the (+)-(S)- and (-)-(R)-enantiomers of mirtazapine was achieved on a Chiralpak AD column (250 mm x 4.6 mm, 10 microm particle size) protected with a CN guard column, using hexane-ethanol (98:2, v/v) plus 0.1% diethylamine as the isocratic mobile phase, at a flow rate of 1.2 ml/min. The total analysis time was less than 12 min per sample. The recoveries of (+)-(S)- and (-)-(R)-mirtazapine were in the 88-111% range with a linear response over the 6.25-625 ng/ml concentration range for both enantiomers. The quantification limit (LOQ) was 5 ng/ml. Within-day and between-day assay precision and accuracy were studied at three concentration levels (10, 50 and 250 ng/ml). For both mirtazapine enantiomers, the coefficients of variation (CV) and deviation from the theoretical value were lower than 15% at all concentration levels. The method proved to be suitable for pharmacokinetic studies.
建立了一种简单、快速、灵敏的高效液相色谱（HPLC）方法，用于对人血浆中新型抗抑郁药物米氮平进行对映体选择性分析。该方法包括用甲苯进行液液萃取，然后进行液相色谱，并在292nm处进行紫外检测。米氮平的（+）-（S）-和（-）-（R）-对映体在Chiralpak AD柱（250mm×4.6mm，粒径10μm）上进行色谱分离，该柱由CN保护柱保护，使用己烷-乙醇（98:2，v/v）加0.1%二乙胺作为等度流动相，流速为1.2ml/min。每个样品的总分析时间少于12分钟。（+）-（S）-和（-）-（R）-米氮平的回收率在88%-111%范围内，两种对映体在6.25-625ng/ml浓度范围内均呈线性响应。定量限（LOQ）为5ng/ml。在三个浓度水平（10、50和250ng/ml）下研究了日内和日间分析的精密度和准确度。对于两种米氮平对映体，所有浓度水平下的变异系数（CV）和与理论值的偏差均低于15%。该方法被证明适用于药代动力学研究。
