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

Vittoria Delbono; Christopher P Larch; Katrina Carol Newlands; Shona Rhydderch; Thomas Craven Baddeley; John Mervyn David Storey

doi:10.1155/2022/9171836

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

TauRx Therapeutics Ltd., Singapore

Research output: Contribution to journal › Article › peer-review

2 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 language	English
Article number	9171836
Number of pages	10
Journal	International journal of analytical chemistry
Volume	2022
DOIs	https://doi.org/10.1155/2022/9171836
Publication status	Published - 6 Sept 2022
Event	2021 Chemistry PGR Symposium - Aberdeen, United Kingdom Duration: 18 Jun 2021 → 25 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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Delbono_etal_IJAC_Novel_Method_of_VOR
Copyright © 2022 Vittoria Delbono et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Final published version, 572 KBLicence: CC BY

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Novel Method of Analysis for the Determination of Residual Formaldehyde by High-Performance Liquid Chromatography. / Delbono, Vittoria (Corresponding Author); Larch, Christopher P (Corresponding Author); Newlands, Katrina Carol et al.
In: International journal of analytical chemistry, Vol. 2022, 9171836, 06.09.2022.

Research output: Contribution to journal › Article › peer-review

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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.",

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AU - Rhydderch, Shona

AU - Baddeley, Thomas Craven

AU - Storey, John Mervyn David

N1 - 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).

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N2 - 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.

AB - 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.

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VL - 2022

JO - International journal of analytical chemistry

JF - International journal of analytical chemistry

M1 - 9171836

T2 - 2021 Chemistry PGR Symposium

Y2 - 18 June 2021 through 25 June 2021

ER -

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

Abstract

Bibliographical note

Data Availability Statement

Keywords

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