摘要
目的建立人血浆中罗红霉素的高效液相色谱测定法，并研究罗红霉素分散片在人体的相对生物利用度。方法以克拉霉素为内标，血浆样品用二氯甲烷（含5％的异丙醇）液-液萃取后经HypersiL BDS C18柱（200mm×4．6mm，5μm）分离，流动相为乙腈-0．5％醋酸铵（46：54，v／v，氨水调pH值至8．0），流速为1mL·min^-1，检测波长：0～6．2min为300nm，6．2～8．0min为207nm。18名健康志愿者采用三周期随机交叉方式单剂量口服罗红霉素分散片试验制剂T1、T2或参比制剂R后不同时间点采血，研究三者的生物等效性。结果罗红霉素与内标分离良好，内源性物质不干扰测定。在0．25-32．0g·mL^-1。罗红霉素浓度与罗红霉素和内标峰面积比线性关系良好（r=0．9992）。方法回收率为96．9％～107．6％（n=5），日内RSD〈6．4％（n=15）、日间RSD〈4．3％（n=15）。单次服用0．3g罗红霉素分散片T1、T2和R的主要药物动力学参数分别为：Cmax为（12．4±10．6）、（13．4±4．8）和（13．7±3．9）μg·mL^-1；Tmax为（1．7±0．3）、（1．8±0．4）和（2．3±0．5）h；AUC0～48为（158．1±42．6）、（157．9±54．2）和（160．1±42．5）μg·h·mL^-1。与R相比，T1的相对生物利用度为100．6％±19．7％；T2的相对生物利用度为98．9％±20．2％。结论该方法简单快速、准确度高、灵敏度与重现性好，可用于罗红霉素在人体内过程研究。T1、T2与R为生物等效制剂。
Objective To establish an HPLC method for the determination of roxithromycin in human plasma and study the bioequivalence of roxithromycin dispersible tablets in healthy volunteers. Methods Clarithromycin was used as the internal standard. Roxithromydn was extracted from the plasma sample with dichloromethane （including 5 % dehydrated alcohol） and separated on a Hypersil BDS C18 column （ 200 mm × 4. 6 mm, 5 μm） with a mobile phase consisting of acetonitrile-0.5 ammonium acetate （46 ： 54, v/v, pH being adjusted to 8.0 with ammonia water）, and the flow rate was 1.0 mL · min^-1. The elute was detected at 300 nm from 0-6.2 min and 207nm from 6. 2-8. 0min. Eighteen male volunteers were given 0. 3 g roxithromycin dispersible tablets T1, T2 or R according to a random crossover design. Plasma samples were obtained and determined by the newly-developed HPLC method, and then the pharmacokinetics and bioavailability were studied. Results Roxithromycin was separated well from the endogenous substance, and the regressive curve was linear （r=0. 999 2） within the range of 0. 25 μg · mL^-1 to 32. 0 μg · mL^-1. The recoveries were within 96. 9%-107.6% （n=15）, and the inter-day and intra-day RSD were less than 6. 4%（n=15） and 4. 3% （n=15） respectively. The main pharmacokinetics of T1 , T2 and R were as follows ： Cmax was （12.4±10.6）, （13.4±4.8） and （13.7±3.9）μg·mL^-1; Tmax was （1.7±0.3）, （1.8±0.4） and （2. 3±0. 5） h; AUC0-48 was （158. 1±42. 6）, （157. 9±54. 2） and （160. 1±42. 5） μg·h·mL^-1. Conclusion The method is simple, sensitive, accurate and reproducible, which is suitable for the study of roxithromycin in vivo. T1, T2 and R are bioequivalent.
出处
《中南药学》
CAS
2007年第6期527-529,共3页
Central South Pharmacy
