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

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.

The Importance of Tracking “Missing” Metabolites: How and Why?

“…Nevertheless, the derivatization can be highly effective in liver microsomal incubation mixtures. 11 Similarly, volatile formaldehyde can be analyzed via GC-MS and can also be derivatized by hydrazines to be monitored and analyzed via LC-MS. 168,169 Unexpected reactive and transient metabolites from bioactivation that are quenched by endogenous small molecules and protein nucleophiles can sometimes be overlooked because the resulting metabolite structure is too large or very different from the parent molecule. Thus, trapping reagents such as GSH (for trapping epoxide, α,βunsaturated carbonyls, and other soft electrophiles), cyanide (for trapping iminium ions), semicarbazide/methoxyamine (for trapping aldehydes and migrated acyl glucuronides), and nucleobases (for epoxide, quinone and aldehyde metabolites) can provide additional data to help elucidate the sites and mechanisms of bioactivation.…”

“…Nevertheless, the derivatization can be highly effective in liver microsomal incubation mixtures . Similarly, volatile formaldehyde can be analyzed via GC-MS and can also be derivatized by hydrazines to be monitored and analyzed via LC-MS. , …”

Identification of Formalin in Food Sold in Ciamis by Thin Layer Chromatography

“…iodine and observed for color visually under UV light. Then the stains and the Rf values of the samples and standards were calculated and then compared (Delbono et al, 2022).…”

Determination of formaldehyde in cosmetic creams using gas chromatography/mass spectrometry analysis and solid‐phase microextraction

“…Several methods and techniques for analyzing FA in various samples, such as blood, food samples, air, and cosmetics, have been discussed in the literature [23]. Techniques such as spectrophotometry, capillary electrophoresis, and electrochemistry are used to measure FA [24].…”