Santoro Maria Inês Rocha Miritello, Fazio Tatiana Tatit, Singh Anil Kumar, Kedor-Hackmann Erica Rosa Maria
Universidade de São Paulo, Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, Caixa Postal 66083, CEP 05315-970, São Paulo, SP, Brazil.
J AOAC Int. 2007 May-Jun;90(3):715-9.
Lamivudine (3TC) and zidovudine (AZT) are systemic antiviral substances extensively used in human immunodeficiency virus (HIV) infected patients. Nowadays, 3TC, AZT, and several other pharmacologically potent pharmaceuticals are manufactured in the same production area. To assure quality of drug products and patient safety, properly validated cleaning methodology is necessary. A carefully designed cleaning validation and its evaluation can ensure that residues of 3TC and AZT will not carry over and cross contaminate the subsequent product. The aim of this study was to validate a simple analytical method for verification of residual 3TC and AZT in equipment used in the production area and to confirm the efficiency of the cleaning procedure. The liquid chromatography method was validated using a Nova-Pak C18 column (3.9 x 150 mm, 4 microm particle size) and methanol-water (20 + 80, v/v) as the mobile phase at a flow rate of 1.0 mL/min. Ultraviolet detection was made at 266 nm. The calibration curve was linear over a concentration range of 2.0-22.0 microg/mL with a correlation coefficient of 0.9998. The detection and quantitation limits were 0.36 and 1.21 microg/mL, respectively. The intra-day and interday precision expressed as relative standard deviation were below 2.0%. The mean recovery of the method was 99.19%. The mean extraction recovery from manufacturing equipment was 83.5%.
拉米夫定（3TC）和齐多夫定（AZT）是广泛用于人类免疫缺陷病毒（HIV）感染患者的全身性抗病毒药物。如今，3TC、AZT以及其他几种具有药理活性的药物都在同一生产区域生产。为确保药品质量和患者安全，需要经过适当验证的清洁方法。精心设计的清洁验证及其评估可以确保3TC和AZT的残留不会残留并交叉污染后续产品。本研究的目的是验证一种简单的分析方法，以验证生产区域所用设备中3TC和AZT的残留，并确认清洁程序的有效性。使用Nova-Pak C18柱（3.9×150 mm，4μm粒径）和甲醇-水（20 + 80，v/v）作为流动相，流速为1.0 mL/min，对液相色谱法进行了验证。在266 nm处进行紫外检测。校准曲线在2.0-22.0μg/mL的浓度范围内呈线性，相关系数为0.9998。检测限和定量限分别为0.36和1.21μg/mL。以相对标准偏差表示的日内和日间精密度均低于2.0%。该方法的平均回收率为99.19%。从生产设备中的平均提取回收率为83.5%。
