盐酸利多卡因眼用凝胶在兔眼房水中药物浓度测定及药动学研究  

Determination and Pharmacokinetics of Lidocaine in Aqueous Humor after Ocular Administration of Lidocaine Hydrochloride Ophthalmic Gel to Rabbits

作　　者：刘冰[1] 徐晓文[1] 林宏达[1] 孙成龙[1] 丁黎[1] 尤淋君[2] 

机构地区：[1]中国药科大学药物分析教研室,南京210009 [2]中国药科大学新药安全评价研究中心,南京210009

出　　处：《药学与临床研究》2014年第3期201-204,共4页Pharmaceutical and Clinical Research

摘　　要：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。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（5 μm, 150mm×2.1 mm i.d.） with a mobile phase of methanol-0.1% formic acid water solution with 20 mmol·L-1ammonium 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-1with r=0.9995. After administration of the test and reference formulation to the rabbits, the Cmaxvalues were（10193±4535） ng·mL-1and（11046±2734） ng·mL-1, respectively, the AUC0-8values were 7582 ng·h·mL-1and 8125 ng·h·mL-1, respectively, the t1/2values 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.

关 键 词：利多卡因 眼用凝胶 房水 药代动力学 新西兰兔 LC-MS MS 

分 类 号：R969.1[医药卫生—药理学]