液质联用测定血浆中阿奇霉素及其人体药动学和相对生物利用度研究

Determination of Azithromycin in Human Plasma by HPLC-MS and Its Relative Bioavailability

目的建立人血浆中阿奇霉素的高效液相色谱-质谱测定方法,用于研究阿奇霉素分散片的人体药动学及相对生物利用度。方法血浆样品中加入内标克拉霉素后,经乙酸乙酯提取,采用高效液相色谱-质谱法,电喷雾电离源选择性正离子峰检测。用建立的方法测定18名健康男性志愿者单剂量口服阿奇霉素分散片实验制剂或参比制剂的体内经时过程,由血药浓度数据获得各自的药动学参数,以双单侧t检验进行生物等效性判定。结果在2．5-800μg·L-1内呈良好的线性关系,r= 0．999 3,平均回收率为98．1％,日内RSD≤11．3％,日间RSD≤8．6％,单次服用500 mg阿奇霉素分散片实验制剂或参比制剂后的药动学参数AUC0-120,ρmax,tmax,t1/2分别为(5 856．5±1 423．6)和(6 096．8±1 111．0)μg·h·L-1,(520．1±94．1)和(558．8± 74．0)μg·L-1,(1．4±0．4)和(1．3±0．2)h,(36．1±10．2)和(36．2±11．7)h。相对生物利用度为(96．3±16．0)％。结论该方法灵敏度高,无杂质干扰,结果准确。测得的实验制剂与参比制剂的主要药动学参数之间无明显差异,两种片剂为生物等效制剂。

OBJECTIVE To determine azithromyein in human plasma by a HPLC-MS method, and to study its relative bioavailability.METHODS Azithromycin concentrations in plasma were determined by HPLC-MS.The test and reference formulations of azithromycin were given to 18 healthy male volunteers. Bioequivalence was determined by a two one-side t-tests.RESULTS The calibration curve was linear within the range of 2.5 - 800μg· L^- 1 （ r = 0.999 3）, the recovery was 98.1%, the RSDs of intm- and inter-day were no more than 11.3 % and 8.6%. After a single oral dose of 500 mg azithromycin test or reference dispersible tablet, the main pharmacokinetic parameters were as follows：AUC0-120（5 856.5 ± 1 423.6） and （6 096.8 ± 1 111.0）μg·h·L^-1 , ρmax（520.1 ± 94.1） and （558.8 ± 74.0） μg·L^-1, tmax（1.4 ± 0.4） and （1.3 ± 0.2） h , t1/2（36.1 ± 10.2） and （36.2 ± 11.7） h, respectively. Relative bioavailability was （96.3 ± 16.0）%. CONCLUSION The method is accurate and sensitive with no endogenous interference. No significant difference exists among the main pharmacokinetic parameters for the test tablets and the reference tablets. The two formulations are bioequivalent.