The decomposition of benzodiazepines during analysis by capillary gas chromatography/mass spectrometry

Abstract

A capillary gas chromatography column directly interfaced to a mass spectrometer was used for the analysis of sixteen benzodiazepines. The thermal stability of the drugs was found to be related to their chemical structure. Nine of the benzodiazepines were thermally unstable indicating that care should be taken in the interpretation of gas chromatographic data from this class of drugs. The unstable benzodiazepines were: ketazolam which decomposes to diazepam; N-4 oxides (chlordiazepoxide and demoxepam) which lose an oxygen radical; aromatic 7-nitro compounds (nitrazepam and clonazepam) which are partially reduced to the corresponding amine; alpha-hydroxy ketones (lorazepam and oxazepam) which decompose with the loss of water and N-methyl-alpha-hydroxy ketones (lormetazepam and temazepam) which partially decompose with the loss of a hydrogen molecule to produce the corresponding alpha, beta-diketones. Few problems were encountered in distinguishing the drugs by their mass spectra, the exceptions being ketazolam which decomposes to diazepam and demoxepam which decomposes to desmethyldiazepam. In general, good spectra were obtained from 20-50 ng of drug injected. However, for those compounds where the decompositions were not quantitative (nitrazepam, clonazepam, lormetazepam, temazepam) detection limits were poor.

Rapid isolation of some antiepileptic hydantoins and their analogues with Sep-Pak C18 cartridges and capillary gas chromatography with splitless injection

“…Benzodiazepines and butyrophenones are easily decomposed during slow flow through narrow-bore capillary columns [9]. However, hydantoins and their analogues have been found to be relatively resistant to heat decomposition during GC analysis and thus narrow-bore capillary GC was preferred to wide-bore capillary GC because of its higher resolution.…”

A rapid solid-phase extraction and HPLC/DAD procedure for the simultaneous determination and quantification of different benzodiazepines in serum, blood and post-mortem blood

“…Current methods for the determination of benzodiazepines available in clinical or forensic chemistry include thin-layer chromatography (TLC) [5,6], gas chromatography often coupled with mass spectrometry (GC/MS) [7][8][9][10][11], immunological methods [12][13][14][15][16] or high-performance liquid chromatography (HPLC) [11,[17][18][19][20][21][22]. The latter technique is particularly suitable for the quantitative determination of substances with intense UV absorption, such as the 1,4-benzodiazepines, particularly since some of these compounds exhibit thermal instability [23,24]. Although its value as a screening method is still controversial, the combination with diode-array detection has to be considered as a highly effective and selective screening method [25,26].…”

Comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC × GC-TOFMS) for drug screening and confirmation

“…Benzodiazepines were not detected in cases 1 and 2 in GC Â GC analyses. Among them is oxazepam (1,4-benzodiazepine), which is known to be thermally labile [37,38] and prone to aging of injector liners and columns [25]. The above reasons explain the absence of oxazepam for GC Â GC analysis, and while it was found in the reference GC-NPD screen, it is not reported in Table 5 GC Â GC data.…”