Sora Daniela Iuliana, Udrescu Stefan, David Victor, Medvedovici Andrei
SC Labormed Pharma S.A., Splaiul Independentei no. 319 E, Bucharest 060044, Romania.
Biomed Chromatogr. 2007 Oct;21(10):1023-9. doi: 10.1002/bmc.845.
Inter- and intra-individual variability of the loratadine (LOR) metabolism in Caucasian subjects was assessed during a bioequivalence study for two pharmaceutical formulations (solid oral dosage forms) containing 10 mg of the active substance. The analytical data were obtained by applying a reliable, low-cost and sensitive ion pair liquid chromatography/fluorescence (IPLC/FLD) method for determination of both loratadine and descarboethoxyloratadine (DCL) in human plasma samples. The sample preparation procedure is based on liquid-liquid extraction of the target analytes from alkalinized plasma using diethyl-ether. The separation of the analytes and 8-chloroazatadine as internal standard (IS) was achieved through an isocratic ion pair (IP) elution on a Purospher((R)) STAR RP-18 column. The mobile phase containing sodium dodecyl sulfate (SDS) as ion pairing agent was pumped at a flow rate of 1 mL/min. Fluorescence detection (FLD) was achieved at 280 nm (excitation) and 440 nm (emission) wavelengths. The increased sensitivity of the method is also based on a large sample injected volume (250 microL). Linear response was found over the 0.5-20 ng/mL concentration interval for both target compounds. Low limits of quantification (LLOQ) around 0.3 ng/mL were found for LOR and DCL. Method validation is presented.
在一项生物等效性研究中，对两种含有10毫克活性物质的药物制剂（固体口服剂型），评估了白种人受试者中氯雷他定（LOR）代谢的个体间和个体内变异性。通过应用一种可靠、低成本且灵敏的离子对液相色谱/荧光（IPLC/FLD）方法，测定人血浆样品中的氯雷他定和去乙氧羰基氯雷他定（DCL），从而获得分析数据。样品制备程序基于使用乙醚从碱化血浆中液-液萃取目标分析物。通过在Purospher((R)) STAR RP-18柱上进行等度离子对（IP）洗脱，实现了分析物与作为内标（IS）的8-氯氮卓斯汀的分离。以1毫升/分钟的流速泵送含有十二烷基硫酸钠（SDS）作为离子对试剂的流动相。在280纳米（激发）和440纳米（发射）波长处进行荧光检测（FLD）。该方法灵敏度的提高还基于较大的进样体积（250微升）。两种目标化合物在0.5-20纳克/毫升浓度区间内呈线性响应。LOR和DCL的定量下限（LLOQ）约为0.3纳克/毫升。给出了方法验证结果。
