title: Quantitative determination and sampling of lamivudine and zidovudine residues for cleaning validation in a production area.
abstract: 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%.
authors.affiliation: Universidade de São Paulo, Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, Caixa Postal 66083, CEP 05315-970, São Paulo, SP, Brazil. ines@usp.br
authors.forename: Maria Inês Rocha Miritello
authors.initials: MI
authors.lastname: Santoro
authors.forename: Tatiana Tatit
authors.initials: TT
authors.lastname: Fazio
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Erica Rosa Maria
authors.initials: ER
authors.lastname: Kedor-Hackmann
mesh_terms: D000998:Antiviral Agents / Q000032:analysis*; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002845:Chromatography; D002853:Chromatography, Liquid / Q000379:methods; D004345:Drug Industry / Q000379:methods*; D004350:Drug Residues / Q000032:analysis*; D019259:Lamivudine / Q000032:analysis*; D000432:Methanol / Q000737:chemistry; D008956:Models, Chemical; D012015:Reference Standards; D012044:Regression Analysis; D015203:Reproducibility of Results; D014867:Water / Q000737:chemistry; D015215:Zidovudine / Q000032:analysis*
chemical_list: D000998:Antiviral Agents; D014867:Water; D019259:Lamivudine; D015215:Zidovudine; D000432:Methanol