Vibrational spectroscopy for discrimination and quantification of clinical chemotherapeutic preparations

Abstract In a clinical setting, analytical quality control of the administration of chemotherapeutic preparations is required to ensure patient safety with respect to the dose and more importantly the correct anticancer drug. As such, analytical tools enabling both qualitative and quantitative verification of the composition of prepared solutions can greatly benefit the hospital workflow, reducing cost and ultimately ensuring optimum patient care and outcome. Raman and infrared spectroscopy are rapid and cost-effective techniques, delivering label free molecular characterisation of samples. A comparative study has been conducted using four commercial intravenous formulations, DOXORUBICINE TEVA®, CERUBIDINE®, HOLOXAN® and METHOTREXATE MYLAN®, respectively containing doxorubicin, daunorubicin, ifosfamide and methotrexate as active drugs. Using clinically relevant concentration ranges prepared in 0.9 % NaCl or 5% glucose solutions, it is demonstrated that 100 % discrimination can be achieved for all formulations using either Raman or IR spectroscopic techniques, combined with multivariate discriminant analysis. Employing a partial least square regression analysis, Raman spectroscopy performed on liquid samples delivers a better accuracy compared to infrared for quantification, based on the mean squared error of cross validation. However, it is demonstrated that, despite the strong contribution of glucose and mannitol, an excipient found in CERUBIDINE®, infrared spectroscopy remains an equally viable option for translation into clinics.