Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA.
Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA; Department of General and Inorganic Chemistry, Medical University of Silesia, Katowice FOPS in Sosnowiec, Poland.
J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Apr 30;1170:122610. doi: 10.1016/j.jchromb.2021.122610. Epub 2021 Mar 1.
The complexity of Tobradex® ointment formulation (dexamethasone 0.1 wt% and tobramycin 0.3 wt%) and the high cost of pharmacokinetic (PK) studies in human aqueous humor may prevent generic drug companies from moving forward with a Tobradex®-equivalent product development. The in vitro drug release test would be an alternative approach for differentiating the generic formulations containing both dexamethasone (DEX) and tobramycin (TOB), and the results should be correlated with the in vivo ocular PK studies for further evaluation. To facilitate the in vivo ocular PK studies, a sensitive, rapid and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method that can simultaneously quantify both DEX and TOB in rabbit ocular matrices including tear, aqueous humor and cornea was established and validated. The lower limit of quantification (LLOQ) was 1.5 ng/ml for DEX and 3 ng/ml for TOB with good precision and accuracy. Both intra- and inter-batch precisions were within ±15%, and the accuracy for all QCs was within the range of 85-115%. This new method was successfully applied for a pilot pharmacokinetic analysis of DEX and TOB in rabbit tears after topical administration of Tobradex® ointment.
特布他林®软膏制剂（地塞米松 0.1wt%和妥布霉素 0.3wt%）的复杂性以及在人房水中进行药代动力学（PK）研究的高昂成本可能会阻止仿制药公司继续开发特布他林®等效产品。体外药物释放试验将是区分含有地塞米松（DEX）和妥布霉素（TOB）的仿制药配方的替代方法，并且结果应与体内眼 PK 研究相关联，以进行进一步评估。为了便于体内眼 PK 研究，建立并验证了一种灵敏、快速和特异的液相色谱-串联质谱（LC-MS/MS）方法，可同时定量兔眼组织中的 DEX 和 TOB，包括泪液、房水和角膜。DEX 的定量下限（LLOQ）为 1.5ng/ml，TOB 的定量下限（LLOQ）为 3ng/ml，具有良好的精密度和准确性。批内和批间精密度均在±15%范围内，所有 QC 的准确度均在 85-115%范围内。该新方法成功地应用于特布他林®软膏局部给药后兔泪中 DEX 和 TOB 的初步药代动力学分析。
