Detection and quantification of low-molecular-weight aldehydes in pharmaceutical excipients by headspace gas chromatography.

The adverse effect of reactive chemical residues on the quality of drug products has necessitated the determination of low-molecular-weight aldehydes in pharmaceutical excipients. An analytical methodology for the detection of trace amounts of C1-C8 aliphatic aldehydes and benzaldehyde in excipients is described. The proposed procedure is based on the derivatization of aldehydes in aqueous solution with O-2,3,4,5,6-(pentafluorobenzyl) hydroxylamine hydrochloride (PFBHA), followed by static headspace gas chromatographic (SHS-GC) analysis of PFBHA aldehyde oximes with negative chemical ionization (NCI) MS detection. The method developed was demonstrated to be simple, selective, sensitive, and was successfully applied to the screening of aldehydes at sub-microg/g levels in over 30 typical excipients. The most abundant aldehydes found in the samples were formaldehyde and acetaldehyde, for which a rapid and reliable routine quantification method by readily available SHS-GC instrumentation coupled with flame-ionization detection was also developed and validated.