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Development of a novel HPLC-DAD-FLD-MS method for the simultaneous determination of five anticancer drugs

Introduction: Palbociclib and ribociclib are newly registered anticancer agents often used in combination with anastrozole, letrozole or fulvestrant for the treatment of breast cancer (1). Novel anticancer medicines are potential candidates for therapeutic drug monitoring in plasma in order to avoid drug-related toxicities and enhance therapeutic outcomes (2). Therefore, it is desirable to employ a simultaneous high performance liquid chromatographic (HPLC) method for the selective determination of these analytes in a complex biological sample. Materials and Methods: Several chromatographic columns were tested, the influence of mobile phase composition and pH was investigated, gradient elution steps, flow rate and column temperature were optimised. Detection was carried out using a diode-array detector (DAD), a fluorescence detector (FLD), and a mass spectrometer (MS). Results: The optimal conditions were as follows: biphenyl column 4.6x150 mm, 2.6 μm, gradient elution with acetonitrile and water, both containing 0.1 % formic acid, as mobile phase, 25 °C column temperature and 0.5 mL/min flow. All peaks eluted within 12 min and adequate separation was accomplished, as presented in the table: Name Retention Time USP Resolution DAD absorption maximum (nm) Main ion ESI+ (m/z) Limit of detection (ng/mL) Ribociclib 4.163 270 435.45 52.2 Palbociclib 4.911 15.0 366 448.41 39.98 Anastrozole 6.904 37.9 210 294.27 19.8 Letrozole 7.114 3.8 240 217.17 16.6 Fulvestrant 8.748 28.2 210 607.67 1.98 Conclusions: A selective and sensitive new HPLC- DAD-FLD-MS method was developed for the simultaneous determination of five anticancer drugs in human plasma.

Breast cancer ; Therapeutic drug monitoring ; HPLC-MS

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