Degradation of a pharmaceutical in HPLC grade methanol containing trace level formaldehyde
Qiqing Zhong1, Sarah Stowers, Nathaniel L Segraves
1Department of Small Molecule Pharmaceutical Sciences, Genentech, Inc. 1 DNA Way, South San Francisco, CA, USA.
Abstract:
An anomalous peak was observed in the HPLC/UV analysis of a developmental drug product. High resolution LC/MS revealed that the mass of this degradant was 12 Da greater than the drug substance, corresponding to a net gain of a single carbon atom. The degradant was reproduced by incubating the drug substance with formaldehyde, followed by isolation using normal phase chromatography and structure elucidation by NMR. It was determined to be an analytical artifact caused by the nucleophilic reaction of the drug substance with trace levels of formaldehyde in the methanol diluent. Typical formaldehyde levels in various grades of methanol were determined, leading to the adoption of spectrophotometric purity solvent to mitigate the recurrence of this artifact. This work demonstrates that even ppm levels of impurities in solvents can cause significant degradation of drug product and the HPLC grade solvents are not always suitable for HPLC analysis in drug product development.
More Related Videos
Related Concept Videos
High-Performance Liquid Chromatography: Elution Process
High-Performance Liquid Chromatography: Instrumentation
High-Performance Liquid Chromatography: Introduction
In HPLC, two phases play a critical role in the separation process:
Multiple Halogenation of Methyl Ketones: Haloform Reaction


