Novel Method of Analysis for the Determination of Residual Formaldehyde by High-Performance Liquid Chromatography

Vittoria Delbono* (Corresponding Author), Christopher P Larch* (Corresponding Author), Katrina Carol Newlands, Shona Rhydderch, Thomas Craven Baddeley, John Mervyn David Storey

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
2 Downloads (Pure)

Abstract

Formaldehyde is commonly used as an alkylating agent in the pharmaceutical industry. Consequently, its residual level in drug substances and/or their intermediates needs to be accurately quantified. Formaldehyde is a small, volatile molecule with a weak chromophore (the carbonyl group), and its direct analysis by GC-FID and HPLC-UV is difficult. For these reasons, the majority of papers found in the literature are based upon a derivatisation process (most commonly using the desensitised explosive 2,4-dinitrophenylhydrazine) prior to the analysis of formaldehyde. A novel high-performance liquid chromatography (HPLC) method with UV detection for its quantification in a pharmaceutical is described in this paper. The method proposed herein is based upon a derivatisation reaction between formaldehyde and 4-methylbenzenesulfonohydrazide (MBSH) before analysis by HPLC-UV. Selectivity, linearity, limit of quantification, accuracy, repeatability, intermediate precision, and solution stability were successfully assessed as per ICH guideline Q2(R1), and the method has also been validated in a good manufacturing practice (GMP) laboratory in the UK.

Original languageEnglish
Article number9171836
Number of pages10
JournalInternational journal of analytical chemistry
Volume2022
DOIs
Publication statusPublished - 6 Sept 2022
Event2021 Chemistry PGR Symposium - Aberdeen, United Kingdom
Duration: 18 Jun 202125 Jun 2021
https://www.abdn.ac.uk/ncs/documents/Final_agenda_and_abstracts_of_2021_Chemistry_PGR_symposium.pdf

Bibliographical note

The authors wish to thank TauRx Therapeutics Ltd. for funding the project and the analytical consultant David Murphy for the valuable discussions on method development and validation.
Disclosure
A part of the data was presented by the author at the 2021 Chemistry PGR symposium at the University of Aberdeen (https://www.abdn.ac.uk/ncs/documents/Final_agenda_and_abstracts_of_2021_Chemistry_PGR_symposium.pdf).

Data Availability Statement

The data used to support the findings of this study are included within the article.

Keywords

  • 2,4-DINITROPHENYLHYDRAZINE
  • AGGREGATION INHIBITOR THERAPY
  • AIR
  • ALDEHYDES
  • CARBONYL-COMPOUNDS
  • DERIVATIZATION
  • FLUOROMETRIC-DETERMINATION
  • HPLC
  • PHARMACEUTICAL EXCIPIENTS
  • QUANTIFICATION

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