摘要
目的建立测定人体血浆中头孢地尼浓度的UPLC-MS/MS方法,评价3种头孢地尼口服药物在健康人体内的生物等效性。方法随机、自身前后三交叉的试验设计。24名健康男性受试者单剂量口服3种头孢地尼100 mg,用UPLC-MS/MS法测定其血药浓度,计算主要药代动力学参数及相对生物利用度,评价3种药物的生物等效性。结果头孢地尼的线性范围为11.50~2300.00ng·m L^-1,批内、批间精密度(RSD)均小于10%。受试药物(片剂,分散片)与参比药物(胶囊)的主要药代动力学参数为,tmax分别为(3.00±0.80),(3.20±0.90)和(3.50±0.70)h;Cmax分别为(548.96±184.58),(607.09±236.38)和(570.18±172.37)ng·m L^-1;t1/2分别为(2.00±0.30),(1.90±0.40)和(1.90±0.30)h,AUC0-t分别为(2755.35±956.10),(3037.49±1014.42)和(2756.43±804.06)ng·m L^-1·h。头孢地尼片和头孢地尼分散片分别以胶囊为对照,相对生物利用度分别为(104.2±37.5)%和(111.8±30.3)%。结论建立的分析方法灵敏、快速、准确。3种头孢地尼在健康人体内的生物等效。
Objective To establish a high performance liquid chroma- tography -tandem mass spectrometry (UPLC -MS/MS) method to determination the plasma concentration of cefdinir and to study the pharmacokinctics and bioequivalence of three kinds of cefdinir formulations in healthy volunteers. Methods In a randomized, 3 way - crossover and selfcontrol study, 24 healthy male volunteers were orally administrated with three kinds of cefdinir formulations ( test sample and reference sample) 100 mg. The concentrations of cefdinir in plasma were determined by LC - MS/MS. The main pharmacokinetic parameters were calculated. Results The method was validated by investigating the accuracy and precision for intra and interday runs in a linear concentration from 11.50 -2300. 00 ng · mL^-1. The main pharmacokinetic parameters of test (cefdinir tables A drug, cefdinir dispersible tables B drug ) and reference (cefdinir capsules, C drug ) formulations in plasma were shown as follows: tmax were (3.00±0.80), (3.20 ±0.90)and (3.50 ±0.70) h ; Cmax were (548. 96 ± 184. 58), (607.09 ± 236. 38) and (570.18 ± 172.37) ng · mL^-1 ;t1/2 were ( 2. 00 ±0.30) ,(1.90 ±0.40)and (1.90 ±0. 30) h; AUC0-t were (2755.35 ±956.10), (3037.49 ±1014.42) and (2756. 43 ± 804.06) ng · mL^-1 · h, respectively. The relative bioavailability F were ( 104.20 ±37.50)% and ( 111.50±29.70) %. Conclusion The method was proved to be accurate, rapid and sensitive. The three kinds of cefdinir formulations are bioequivalent in healthy volunteers.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2015年第15期1516-1518,1535,共4页
The Chinese Journal of Clinical Pharmacology