Identification of Degradation Products in Cyclophosphamide API by LC-QTOF Mass Spectrometry

Abstract

A rapid, specific, and novel gradient LC–MS method has been developed for the identification of degradation products (DPs) of cyclophosphamide (CY) under different stress conditions using liquid chromatography combined with quadrupole time-of-flight electrospray ionization tandem mass spectrometry (LC-QTOF–ESI-MS/MS). CY was subjected to hydrolytic (acidic, alkaline, and neutral) as per ICH guidelines Q1A (R2). The drug showed extensive degradation in hydrolytic stress conditions. In total, eight DPs were formed, and the chromatographic separation of drug and its DPs was achieved on a C-8 column (2.1 × 100 mm, 1.7 µm) using gradient elution method. The elemental composition of the degradation products was elucidated by using LC–ESI–MS/MS combined with accurate mass measurements.

Keywords:

• cyclophosphamide
• degradation studies
• ESI
• ICH guidelines
• QTOF
• UPLC

Acknowledgments

The authors wish to thank Waters India for providing the analytical equipment and encouragement.

Notes

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