title: Development and application of a validated gradient elution HPLC method for simultaneous determination of 5-fluorouracil and paclitaxel in dissolution samples of 5-fluorouracil/paclitaxel-co-eluting stents.
abstract: The combined use of 5-fluorouracil and paclitaxel is common in clinical trials. However, there are few methods for simultaneous determination of 5-fluorouracil and paclitaxel; most reported approaches can only quantitate either 5-fluorouracil or paclitaxel. This paper proposes a new gradient elution HPLC method for simultaneous determination of 5-fluorouracil and paclitaxel using a photodiode array detector, C₁₈ column (250 mm × 4.6 mm, 5 μm) with methanol and 0.5% H₃PO₄ aqueous solution as the mobile phase components. The injection volume was 50 μl and the column temperature was maintained at 30 °C. The method was validated according to USP Category I requirements. The validation characteristics included system suitability, linearity, analytical range, LOD, LOQ, accuracy, precision, specificity, stability, ruggedness and robustness. The calibration curves exhibited linear concentration ranges of 0.2-40 μg/ml for 5-fluorouracil and 1.5-150 μg/ml for paclitaxel with correlation coefficients larger than 0.99990. The lower limits of quantitation were 2 ng/ml for 5-fluorouracil and 0.75 μg/ml for paclitaxel, respectively. The intra and inter-day precision and accuracy were found to be well within acceptable limits (i.e., 5%). The results demonstrate that this method is reliable, reproducible and suitable for simultaneous quantitation of the two drugs in the release media of 5-fluorouracil/paclitaxel-co-eluting stents.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Weiluan
authors.initials: W
authors.lastname: Chen
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shen
authors.forename: Haojun
authors.initials: H
authors.lastname: Rong
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: Shengrong
authors.initials: S
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D004355:Drug Stability; D054855:Drug-Eluting Stents; D005472:Fluorouracil / Q000008:administration & dosage / Q000032:analysis*; D057230:Limit of Detection; D016014:Linear Models; D017239:Paclitaxel / Q000008:administration & dosage / Q000032:analysis*; D012015:Reference Standards; D015203:Reproducibility of Results; D012995:Solubility; D012996:Solutions
chemical_list: D000970:Antineoplastic Agents; D012996:Solutions; D017239:Paclitaxel; D005472:Fluorouracil