人血浆中特非那定的LC-MS测定法

Determination of terfenadine concentration in human plasma by LC-MS

目的:建立人血浆中特非那定的高效液相色谱-电喷雾质谱联用(HPLC/ESI-MS)测定方法。方法:以氟桂利嗪为内标,血浆以2 mol/L NaOH溶液碱化后,经乙酸乙酯提取;选用PhenomenexC18色谱柱(250 mm×4.6 mm,5μm),柱温25℃;流动相为甲醇-水80∶20(含1%的冰醋酸和0.5%的三乙胺),流速1 mL/min;采用四级杆电喷雾质谱检测器进行定量,选择性正离子检测(SIM),特非那定m/z472,氟桂利嗪m/z203。结果:本法线性范围为0.1～20 ng/mL,最低检测限为0.05 ng/mL(S/N>3),血浆中特非那定的日内和日间精密度为2.54%～9.28%,回收率为88.62%～91.67%。结论:本法专属性强、灵敏度高,适用于临床试验中特非那定的药代动力学研究。

AIM： To establish a highly sensitive method for the quantitation of terfenadine in human plasma by using high performance liquid chromatogramelectrospray ionization-mass spectrometry （ LC-ESI- MS）. METHODS： Flunarizine was chosen as the internal standard （ I. S. ）, the plasma was extracted by ethyl acetate after alkalized with 2 mol/L sodium hydroxide, and the Phenomenex C18 chromatographic column（250 mm ×4.6 mm, 5 μm）was used, the column temperature was 25 ℃, the mobile phase was methanol-water （ 80 ： 20） including 1% glacial acetic acid and 0.5 % triethylamine. The flow rate was 1 mL/ rain. Analytes were quantitated using positive electrospray ionization in a quadrupole spectrometer. The se-lected ion monitoring（SIM） mode was detected , terfenadine m/z was 472 and flunarizine m/z was 203. RESULTS： The linear range was 0.1 - 20 ng/mL, the lowest detectable limit was 0.05 ng/mL （S/N 〉 3）, The intra and inter=assay precision of terfenadine was 2.54 % - 9.28 %. The recovery of terfenadine in plasma was 88.62 % - 91.67%. CONCLUSION： The method has strong specificity and high sensitivity and can be used for clinical experiment of terfenadine pharmacokinetic study.