Direct Quantitation of Formaldehyde in Pressurised Metered Dose Inhaler (pMDI) Devices.

Mike Ludlow, Kathryn Arthur, Paula Dunster, Phil Teale

A direct sampling procedure has been successfully developed for the derivatisation of residual levels of formaldehyde in pressurised metered dose inhaler (pMDI) devices, enabling total quantitation using standard high performance liquid chromatography coupled with ultra-violet detection (HPLC-UV).
The potential presence of formaldehyde, which can be derived from a range of commonly utilised polymeric components, is a particular area of concern for high exposure risk drug delivery systems such as pMDI devices1,2.
Formaldehyde is toxic, allergenic and is a known human carcinogen. The compound is also highly reactive and has the potential to adversely interact with the active pharmaceutical ingredient (API) or other excipient components. This can cause issues in terms of product safety and have a negative impact on the overall efficacy of the drug product.
The short term exposure limit for formaldehyde is under review and is likely to be reduced from the current level of 2 parts per million (ppm)3. In order to assess the viability of current sampling methodologies a study was performed where placebo pMDI devices were spiked with known amounts of formaldehyde around the level of concern. The results from this study showed that existing procedures would not be suitable.
The developed method has been fully validated in accordance with ICH guidelines and is capable of sub μg / canister detection levels, in a range of generic drug product formulations, with a limit of detection (LOD) of 0.55 μg / canister and reproducibility typically <2% RSD.

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