药学与临床研究
藥學與臨床研究
약학여림상연구
PHARMACEUTICAL AND CLINICAL RESEARCH
2014年
3期
201-204
,共4页
刘冰%徐晓文%林宏达%孙成龙%丁黎%尤淋君
劉冰%徐曉文%林宏達%孫成龍%丁黎%尤淋君
류빙%서효문%림굉체%손성룡%정려%우림군
利多卡因%眼用凝胶%房水%药代动力学%新西兰兔%LC-MS/MS
利多卡因%眼用凝膠%房水%藥代動力學%新西蘭兔%LC-MS/MS
리다잡인%안용응효%방수%약대동역학%신서란토%LC-MS/MS
Lidocaine%Ophthalmic gel%Aqueous humor%Pharmacokinetics%New Zealand rabbits%LC-MS/MS
目的:建立兔眼房水中利多卡因的LC-MS/MS检测方法,研究盐酸利多卡因眼用凝胶在兔眼房水中的药动学特征。方法:72只雄性新西兰兔分成Ⅰ和Ⅱ两组,每组36只,Ⅰ和Ⅱ组分别给予盐酸利多卡因眼用凝胶受试制剂和参比制剂,左右眼均滴入15μL,于不同时间点取房水样品,经沉淀蛋白后,采用LC-MS/MS法测定房水中的利多卡因。以来曲唑为内标,采用Hanbon Hedera ODS-2 C18(2.1 mm×150 mm,5μm)色谱柱,流动相为甲醇-20 mmol·L-1醋酸铵水溶液(含0.1%甲酸)(55∶45,v/v),质谱采用气动辅助电喷雾离子化和正离子多重反应监测。结果:利多卡因房水浓度在2.070~10350 ng·mL-1范围内线性关系良好(r=0.9995)。单次给予新西兰兔受试制剂和参比制剂后,房水中利多卡因的Cmax分别为(10193±4535) ng·mL-1和(11046±2734) ng·mL-1,AUC0-8分别为7582 ng·h·mL-1和8125 ng·h·mL-1,t1/2分别为2.6 h和1.9 h,Tmax均为0.3 h。结论:盐酸利多卡因眼用凝胶受试和参比制剂在房水中药动学特征一致,眼部给药后利多卡因可快速穿透角膜到达房水,并在房水中达到较高的浓度。
目的:建立兔眼房水中利多卡因的LC-MS/MS檢測方法,研究鹽痠利多卡因眼用凝膠在兔眼房水中的藥動學特徵。方法:72隻雄性新西蘭兔分成Ⅰ和Ⅱ兩組,每組36隻,Ⅰ和Ⅱ組分彆給予鹽痠利多卡因眼用凝膠受試製劑和參比製劑,左右眼均滴入15μL,于不同時間點取房水樣品,經沉澱蛋白後,採用LC-MS/MS法測定房水中的利多卡因。以來麯唑為內標,採用Hanbon Hedera ODS-2 C18(2.1 mm×150 mm,5μm)色譜柱,流動相為甲醇-20 mmol·L-1醋痠銨水溶液(含0.1%甲痠)(55∶45,v/v),質譜採用氣動輔助電噴霧離子化和正離子多重反應鑑測。結果:利多卡因房水濃度在2.070~10350 ng·mL-1範圍內線性關繫良好(r=0.9995)。單次給予新西蘭兔受試製劑和參比製劑後,房水中利多卡因的Cmax分彆為(10193±4535) ng·mL-1和(11046±2734) ng·mL-1,AUC0-8分彆為7582 ng·h·mL-1和8125 ng·h·mL-1,t1/2分彆為2.6 h和1.9 h,Tmax均為0.3 h。結論:鹽痠利多卡因眼用凝膠受試和參比製劑在房水中藥動學特徵一緻,眼部給藥後利多卡因可快速穿透角膜到達房水,併在房水中達到較高的濃度。
목적:건립토안방수중리다잡인적LC-MS/MS검측방법,연구염산리다잡인안용응효재토안방수중적약동학특정。방법:72지웅성신서란토분성Ⅰ화Ⅱ량조,매조36지,Ⅰ화Ⅱ조분별급여염산리다잡인안용응효수시제제화삼비제제,좌우안균적입15μL,우불동시간점취방수양품,경침정단백후,채용LC-MS/MS법측정방수중적리다잡인。이래곡서위내표,채용Hanbon Hedera ODS-2 C18(2.1 mm×150 mm,5μm)색보주,류동상위갑순-20 mmol·L-1작산안수용액(함0.1%갑산)(55∶45,v/v),질보채용기동보조전분무리자화화정리자다중반응감측。결과:리다잡인방수농도재2.070~10350 ng·mL-1범위내선성관계량호(r=0.9995)。단차급여신서란토수시제제화삼비제제후,방수중리다잡인적Cmax분별위(10193±4535) ng·mL-1화(11046±2734) ng·mL-1,AUC0-8분별위7582 ng·h·mL-1화8125 ng·h·mL-1,t1/2분별위2.6 h화1.9 h,Tmax균위0.3 h。결론:염산리다잡인안용응효수시화삼비제제재방수중약동학특정일치,안부급약후리다잡인가쾌속천투각막도체방수,병재방수중체도교고적농도。
Objective: To establish an LC-MS/MS method for the determination of lidocaine in ocular aqueous humor of rabbit and to study the pharmacokinetics of lidocaine hydrochloride ophthalmic gel after a single topical ocular administration. Methods: Seventy-two rabbits were placed in two groups based on the test and reference formulations. Rabbits in each group were instilled with a single 15 μL of lidocaine hydrochloride ophthalmic gel into each eye. Following the sample collection and deproteinization procedures, the lidocaine concentrations in aqueous humor were determined by LC-MS/MS. Letrozole was used as the internal standard and the chromatographic separation was achieved on a Hedara ODS-2 column (5μm, 150 mm×2.1 mm i.d.) with a mobile phase of methanol-0.1% formic acid water solution with 20 mmol·L-1 am-monium acetate(55∶45, V/V). The detection was performed using the electrospray ionization(ESI) operating in the positive ion multiple reaction monitoring(MRM) mode. Results: The method demonstrated good linearity ranged from 2.070 to 10350 ng·mL-1 with r=0.9995. After administration of the test and reference formula-tion to the rabbits, the Cmax values were (10193±4535) ng·mL-1 and (11046±2734) ng·mL-1, respectively, the AUC0-8 values were 7582 ng·h·mL-1 and 8125 ng·h·mL-1, respectively, the t1/2 values were 2.6 h and 1.9 h, respectively, and the Tmax values were both 0.3 h. Conclusion: There was no significant difference of pharmacokinetic characteristics between the two formulations. Lidocaine hydrochloride ophthalmic gel could rapidly achieve a high concentration in aqueous humor after its topical ocular administration to rabbits.