Quantification of oxaliplatin- and ioversol-related compounds in pharmaceutical formulations using novel HPLC-ICP-MS methods.

ABSTRACT

PURPOSE: Accurate quantifying of drug-related compounds in medicines is vital for safety. Commonly used structure-dependent methods rely on analytical standards. High-performance liquid chromatography coupled with inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) offers a promising solution, being structure-independent and not requiring standards. In this study, we aim to develop HPLC-ICP-MS methods for the determination of related compounds in oxaliplatin and ioversol injections. RESULTS: The target analytes were eluted on an XSelect HSS T3 column (2.1 ×50 mm, 5 µm). Specifically, oxaliplatin injection was eluted isocracially for 3.5 min, and ioversol injection was eluted gradient with a total chromatographic run time of 12 min. The measurements to determine dihydroxy oxaliplatin-Pt(IV) and two related compounds of ioversol were performed by monitoring at m/z for 195Pt and 127I, respectively. The calibration curves were established over the range of 0.05-1 µM for Pt and 0.3-15 µM for I with the correlation coefficients greater than 0.999. The limits of quantification were 0.004 µM for dihydroxy oxaliplatin-Pt(IV), 0.022 µM for ioversol related compound A and 0.026 µM for ioversol related compound B. The accuracy (recovery between 93-105%) and precision (repeatability ≤ 6.1% RSD) were fit-for-purpose for dihydroxy oxaliplatin-Pt(IV), and the accuracy (recovery between 95-107%) and precision (repeatability ≤ 3.9% RSD) were also fit-for-purpose for both ioversol related compound A and ioversol related compound B. CONCLUSION: The quantitation accuracy of HPLC-ICP-MS closely matched that of the standard HPLC-UV approach. HPLC-ICP-MS can be used as a complementary analytical technique for quantitative determination of drug-related compounds.