Simultaneous analysis of various anticancer drugs by supercritical fluid chromatography-mass spectrometry. Part II: Method validation and comparison with liquid chromatography

A complete SFC-MS/MS method validation enabling the simultaneous trace-level analysis of 27 conventional anticancer drugs (CADs) was performed. The selected drugs were the following: 5-fluorouracil, azacitidine, busulfan, carboplatin, cisplatin, cyclophosphamide, cytarabine, dacarbazine, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, gemcitabine, idarubicin, ifosfamide, irinotecan, methotrexate, mitomycin, oxaliplatin, paclitaxel, pemetrexed, raltitrexed, topotecan, treosulfan, vinblastine and vincristine. Accuracy profiles were obtained for all CADs. Trueness ranged between 71.0% and 119.8%, while repeatability (1.3-17.5%) and intermediate precision (2.0-24.9%) were determined for all compounds, with limits of quantification comprised between 0.1 and 25 ng.mL^-1. These results were systematically compared with those obtained during the validation of a reference UHPLC-MS/MS method routinely used to analyze 25 of the 27 CADs contained in samples collected from work surfaces in a hospital pharmacy chemotherapy compounding unit. SFC-MS/MS method offered greater accuracy but was hampered by lower precision than the UHPLC-MS/MS method for most of the compounds. Furthermore, although the developed SFC-MS/MS method was characterized by a lower sensitivity, it allowed the quantification of compounds that were difficult to analyze by UHPLC-MS/MS, such as azacitidine and cisplatin, with analytical performance comparable to that obtained for the other CADs analyzed. This feature highlights the complementarity of the two chromatographic approaches in the context of CAD determination in a hospital environment.