LAUSR

HighlightsA generic UHPLC‐MS method development workflow was proposed for the analysis of antineoplastic drugs.Screening, optimization, virtual refinement and virtual robustness testing were done.Limited handling of toxic compounds was required to perform the whole method development.Complete separation of 24 antineoplastic drugs was achieved. Abstract This study reports the use of retention modeling software for the successful method development of 24 injectable antineoplastic agents. Firstly, a generic screening of several stationary and mobile phases (using various organic modifiers and pH) was achieved. Then, an optimization procedure of mobile phase temperature, gradient profile and mobile phase binary composition was conducted through only 28 real experiments using retention modeling software for data treatment. Finally, the optimized separation was achieved with a mobile phase consisting in 10 mM acetic acid at pH 5.1 (A) and acetonitrile (B). A Waters CORTECS® T3 column (100 × 2.1 mm, 1.6 &mgr;m) operated at 25 °C with a gradient time of 17.5 min (0–51%B) at a flow rate of 0.4 mL/min was used. The prediction offered by the retention model was found to be highly reliable, with an average error lower than 1%. A robustness testing step was also assessed from a virtual experimental design. Success rate and regression coefficient were evaluated without the need to perform any real experiment. The developed LC–MS method was successfully applied to the analysis of pharmaceutical formulations and wiping samples from working environment.