止血带下克林霉素在兔肌肉组织中的分布特性

Distribution of Clindamycin in Muscle of Rabbit with Tourniquet

目的建立高效液相色谱法测定兔肌肉组织中的克林霉素,并对止血带下肌肉组织中克林霉素的分布特征进行研究。方法色谱条件为乙腈-四氢呋喃-磷酸盐缓冲液（30∶1∶70,pH=5）为流动相;柱温：40℃;流速：0.8mL·min^-1;替硝唑为内标,LunaC18柱（250mm×4.6mm,5μm）进行分离,检测波长为205nm。测定静脉注射克林霉素30,60,90,120min后上止血带分别阻断血液循环30,60,90min实验组与未止血对照组的肌肉组织中药物含量。结果克林霉素在10.58-264.5μg·mL^-1内线性关系良好,日内RSD≤2.58%,日间RSD≤4.20%。实验组克林霉素含量与对照组比较,P〈0.01;相同止血时机,不同止血时间药物含量比较,P〉0.05;不同止血时机（30,60,90,120min）药物含量比较,P〈0.01;给药后60min上止血带阻断肢体血液循环,克林霉素在肌肉组织的含量最高,为39.30μg·g^-1。结论方法准确可靠、简便、重复性好;实验组克林霉素含量与对照组有显著性差异;围手术期预防感染,上止血带时机是影响克林霉素组织分布的主要因素,给药后60min止血,药物可充分分布到肌肉软组织中,提高预防感染效果。

OBJECTIVE To establish an HPLC method to determine the content of clindamycin in muscle of rabbits, and to study its characteristics of distribution in muscle tissue of rabbits which were stopped bleeding by tourniquet. METHODS The mobile phase consisted of a mixture of acetonitrile-tetrahydrofuran-phosphoric acid（30∶1∶70, pH=5） with a flow rate of 0.8 mL·min-1. Tinidazole was used as an internal standard, the analytical column was packed with 5 μm C18 at 40 ℃, and the detection wavelength was 205 nm. Experiment groups were stopped bleeding for 30, 60, 90 min after drug administration at 30, 60, 90, 120 min, respectively. Then, clindamycin in muscle of exeriment and control groups were determined by HPLC. RESULTS The calibration curve of clindamycin was linear in the range of 10.58-264.5 μg·mL-1. The RSD of intra and inter-day were smaller than 2.58% and 4.20%, respectively. The concentration of clindamycin in exeriment group compared with that in control group was significant different（P〈0.01）. In the same stopped bleeding occasion groups, multiple comparison among the different time length of stopping bleeding groups was not significant different （P〉0.05）, multiple comparison among the different occasion of stopping bleeding groups （30, 60, 90, 120 min） was significant different （P〈0.01）. The concentration of clindamycin was 39.30 μg·g-1 in the group stopped bleeding after drug administration at 60 min, it is the highest content in exeriment groups. CONCLUSION This method is accurate, reliable, simple and reproducible. The difference of concentrations of clindamycin in experiment groups compared with that in control groups is significant. Preventing infection in perioperative period, the occasion of stopping bleeding is the principal factor to affect the distribution of clindamycin in muscle tissue, stopping bleeding after drug administration at 60 min can make medicine distribute to muscle tissue completely, and enhance the efficiency of infection prevention.