title: Application of validated RP-HPLC method for simultaneous determination of docetaxel and ketoconazole in solid lipid nanoparticles.
abstract: Docetaxel has significant single agent activity in prostate cancer and ketoconazole also has activity as a second line hormonal agent. In vitro, ketoconazole is synergistic with some chemotherapy agents by enhancing the intracellular retention of the cytotoxic agent. A potential drug-drug interaction exists though between docetaxel and ketoconazole because both agents are metabolized hepatically by the cytochrome P-450 system. Hence, a nanoparticulate system was formulated by loading both drugs for tumor targeting. Assay and in vitro release of the formulation were conducted by developing simple, precise, accurate, and validated analytical method for simultaneous determination docetaxel and ketoconazole using reversed-phase high-performance liquid chromatography (RP-HPLC). The RP-HPLC method was developed using Waters Symmetry C(18) column (25 cm × 4.5 mm, 5 μm) with a mobile phase consisting of acetonitrile and 0.2% triethylamine pH adjusted to 6.4 (48:52, v/v) at flow rate of 1 mL/min. Intra-day and inter-day variations were less than 2% over the linearity range, 0.5-20 μg/mL. The proposed two methods were successfully applied for the determination of docetaxel and ketoconazole in solid lipid nanoparticles.
authors.affiliation: Pharmacology Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad, Andhra Pradesh, India.
authors.forename: Vinay Kumar
authors.initials: VK
authors.lastname: Venishetty
authors.forename: Nirali
authors.initials: N
authors.lastname: Parikh
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
authors.forename: Farhan J
authors.initials: FJ
authors.lastname: Ahmed
authors.forename: Prakash Vamanrao
authors.initials: PV
authors.lastname: Diwan
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods; D000077143:Docetaxel; D016503:Drug Delivery Systems; D004355:Drug Stability; D007654:Ketoconazole / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D016018:Least-Squares Analysis; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D043823:Taxoids / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D008055:Lipids; D043823:Taxoids; D000077143:Docetaxel; D007654:Ketoconazole