目的 建立測定人血漿中頭孢地尼的液相色譜-串聯(lián)質譜(LC-MS/MS)方法,并用于評價頭孢地尼顆粒在人體的生物等效性。方法 24名健康男性受試者隨機交叉單劑量口服頭孢地尼顆粒受試制劑和參比制劑100 mg,采用LC-MS/MS法測定人血漿樣本中頭孢地尼,WinNonlin 6.3軟件計算其藥動學參數(shù),并評價兩種制劑的生物等效性。結果 血漿中頭孢地尼的線性范圍為10.0~2000 ng/mL(r=0.9997),定量下限為10.0 ng/mL;批內、批間精密度(RSD)均小于6.0%,準確度(RE)在±4.0%以內;隨著放置時間的延長,血漿中頭孢地尼在室溫條件下降解程度增加。受試制劑和參比制劑的AUC_0-t分別為(6238.22±1993.74)、(6331.35±1850.42)ng·h/mL,AUC_0-∞分別為(6343.68±2070.73)、(6429.76±1901.33)ng·h/mL,C_max分別為(1290±391)、(1330±384)ng/mL,t_max分別為2.50(2.00~4.50)、2.50(2.00~3.50)h,t_1/2分別為(1.61±0.17)、(1.61±0.17)h。AUC_0-t、AUC_0-∞和C_max的幾何平均數(shù)比值(GMR)分別為97.88%、97.95%、96.75%,其90%置信區(qū)間分別為91.75%~104.42%、91.76%~104.56%、90.43%~103.52%。結論 該方法快速、靈敏、準確、專屬性強、重現(xiàn)性好,適用于人血漿頭孢地尼的測定。頭孢地尼顆粒受試制劑和參比制劑具有生物等效性。

Objective To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of cefdinir in human plasma and evaluate the bioequivalence of its two granules. Methods A single oral dose of 100 mg cefdinir test and reference granules were given to 24 healthy male volunteers in a randomized, two-way crossway study. The concentrations of cefdinir in plasma were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by WinNonlin 6.3 Software, and the bioequivalence of the two preparations was evaluated. Results The linear range for determining cefdinir in plasma samples was 10.0-2000 ng/mL (r=0.999 7), with the lower limit of quantification (LLOQ) of 10.0 ng/mL. The intra-and inter-batch relative standard deviation (RSD) was lower than 6.0%, and relative error (RE) was within±4.0%. Degradation degree of cefdinir in human plasma was increased under the room temperature storage with the extension of storage time. The main pharmacokinetic parameters of test and reference preparations were as follows: AUC_0-t were (6238.22±1993.74) and (6331.35±1850.42) ng·h/mL; AUC_0-∞ were (6 343.68±2070.73) and (6429.76±1901.33) ng·h/mL; C_max were (1290±391) and (1330±384) ng/mL; t_max were 2.50 (2.00-4.50) h and 2.50 (2.00-3.50) h; t_1/2 were (1.61±0.17) and (1.61±0.17) h, respectively. The geometric mean ratios (GMRs) for AUC_0-t, AUC_0-∞, and C_max were 97.88% (90% CI, 91.75%-104.42%), 97.95% (90% CI, 91.76%-104.56%) and 96.75% (90% CI, 90.43%-103.52%), respectively. Conclusion The established method is rapid, sensitive, accurate, selective, reliable, and sufficient for the determination of cefdinir in human plasma, andthe two preparations are bioequivalent.