摘要
目的建立简便、高效的HPLC—UV法测定大鼠血浆中头孢吡肟的血药浓度，并研究不同剂量的黄芩苷和绿原酸单体给药1周后对头孢毗肟的药动学影响。方法选用SPF级6的SD大鼠，随机分为空白对照组（0．4ml／100g体质量生理盐水）、黄芩苷高、中、低（185、92．5、46．25mg·kg^-1·d^-1）剂组、绿原酸高、中、低（12．33、6．17、3．08mg·kg^-1·d^-1）剂组，尾静脉注射给药7d，末次0．5h后给头孢吡肟，HPLC—uV法测定各时间点头孢吡肟的血药浓度。色谱条件：PhenomenexC18（Luna，5μm，250mm×4．6mm）色谱柱，流动相：乙腈：0．05％甲酸水溶液，柱温：25℃，流速：1ml·min^-1梯度洗脱，在uV=254nm下检测。采用PK—Solution2．0软件计算头孢吡肟的药动学参数。结果头孢吡肟的线性范围为0．125～750mg·L^-1。内线性关系良好，最低检测限（LOD）为0．037mg·L^-1，专属性、准确度、精密度符合生物样品处理要求。与空白组比较，黄芩苷或绿原酸单体高剂量与头孢吡肟合用后，头孢吡肟曲线下面积AUC。和AUC0-∞明显增加（P〈0．01），头孢吡肟的消除半衰期殛明显延长（P〈0．01）。结论该方法专属性强、灵敏度高、准确性好，可用于头孢吡肟的含量测定及药动学研究；黄芩苷或绿原酸单体能延长头孢吡肟在体内代谢的过程。
Aim To develop a sensitive and efficient HPLC-UV method for determination the blood drug concentration of cefepime in plasma of rats, and to study pharmacokinetic effects of single dose of cefepime in combination with using baicalin and chlorogenic acid monomer a week. Methods The SD rats were ran- domly divided into blank control group （0. 4 ml/100 g wet normal saline）, high, medium and low （185, 92.5,46.25 mg · kg^-1· d^-1） dose group of baica- lin, high,middle and low （12.33, 6. 17, 3.08 mg · kg^-1· d^-1） dose group of chlorogenic acid, and it was injected 7 days by tail intravenous, after the last 0.5 h injecting cefepime. HPLC-UV method was used to de- termine the each time point of cefepime blood drug concentration. Chromatographic conditions ： Phenome- nex Cls（Luna, 5 μm, 250 mm ×4.6 ram） chromato- graphic column, mobile phase ： acetonitrile ： 0. 0005 formic acid aqueous solution, and column temperature： 25 ℃, the flow rate： 1 ml ·min^-1 gradient elution, under = 254 nm UV detection. PK_Solution 2.0 software was applied to calculate the pharmacokinetic pa- rameters of cefepime. Results The linear range of cefepime was 0. 125 -750 mg ·L^-1 and the relation- ship was good. Specificity, accuracy and precision met the requirements, good the lowest limit of quantification （LOQ） of cefepime was 0.037 mg ·L^-1 Compared with blank group, the area under curve of cefepime AUC0-t and AUC0-∞ was greatly increased （P 〈 0. 01 ）, and the elimination half-life of cefepime extended significantly （ P 〈 0. 01 ） , with cefepime in combination with baicalin or chlorogenic acid monomer. Conclusions A specific, accurate and precise method is well suitble for content determination of cefepime and pharmacokinetic studies; chlorogenic acid and ba- icalin monomer have been proved to prolong cefepime in the metabolic process, and also have increased the AUC0-t and AUC0 -∞ of cefepime.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2013年第10期1453-1456,共4页
Chinese Pharmacological Bulletin
基金
广东省"211工程"三期重点学科建设项目"药物警戒系统中的中药再评价研究"专项基金[粤发改社(2009)972号文件]
