Degradation of a pharmaceutical in HPLC grade methanol containing trace level formaldehyde.

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.

journal_name

Pharm Dev Technol

authors

Zhong Q,Stowers S,Segraves NL,Ngim KK,Zhang K,Bostick T,Deese A,Chetwyn NP

doi

10.3109/10837450.2012.696265

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

877-82

issue

4

eissn

1083-7450

issn

1097-9867

journal_volume

18

pub_type

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