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目的:建立人血浆中特比萘芬浓度的LC-MS/MS测定方法,并评价特比萘芬的药动学特征及2种制剂的人体生物等效性比较。方法:采用LC-MS/MS法测定特比萘芬的浓度,色谱柱为Diamonsil C18(2)(4.6 mm×150 mm,5μm),流动相为甲醇-20mmol.L-1醋酸铵溶液(含0.1%甲酸)=80∶20,质谱采用MRM模式,检测离子为特比萘芬292.2→140.8,克霉唑为277.2→164.9。20名男性健康受试者随机分成2组,分别交叉给予受试制剂和参比制剂各0.25 g,估算特比萘芬的药动学参数并评价2种制剂的人体生物等效性。结果:人血浆中特比萘芬在2～2 000 ng.ml-1范围内线性关系良好,定量下限为2.0ng.ml-1,批内及批间精密度RSD<15%。受试制剂与参比制剂的各主要药动学参数:tmax分别为(1.2±0.6)和(1.7±0.8)h,Cmax分别为(904.4±272.7)和(831.3±307.0)ng.ml-1,t1/2分别为(20.9±3.4)和(27.1±6.6)h,用梯形法计算AUC(0～∞)分别为(3 951±894.7)和(4 764±2 501)ng.h.ml-1。结论:该方法适用于血浆中特比萘酚的检测。结果显示2种制剂生物等效。
OBJECTIVE: To establish a LC-MS / MS method for the determination of terbinafine in human plasma and to evaluate the pharmacokinetics of terbinafine and compare the bioequivalence of two preparations. Methods: The concentration of terbinafine was determined by LC-MS / MS. Diamonsil C18 (2) (4.6 mm × 150 mm, 5 μm) was used as the mobile phase. The mobile phase consisted of methanol-20 mmol.L-1 ammonium acetate solution 0.1% formic acid) = 80:20, and the MRM mode was adopted for mass spectrometry. The detected ions were terbinafine 292.2 → 140.8, clotrimazole 277.2 → 164.9.20 male healthy subjects were randomly divided into two groups, Formulation and reference formulation 0.25 g each, the pharmacokinetic parameters of terbinafine were estimated and the bioequivalence of the two formulations evaluated. Results: Terbinafine in human plasma showed a good linearity within the range of 2 ~ 2,000 ng · ml-1 with a lower limit of quantitation of 2.0 ng · ml-1. The intra-assay and inter-assay RSDs were less than 15%. The main pharmacokinetic parameters of test and reference preparations were: tmax = (1.2 ± 0.6) and (1.7 ± 0.8) h, and Cmax = (904.4 ± 272.7) and (831.3 ± 307.0) ng.ml-1 , and t1 / 2 were (20.9 ± 3.4) and (27.1 ± 6.6) h, respectively. The trapezoidal method was used to calculate the AUC values of (0 95) ± (3 951 ± 894.7) and (4764 ± 2 501) -1. Conclusion: This method is suitable for the detection of terbinafine in plasma. The results showed that both formulations were bioequivalent.