Determination of benzodiazepines via gas chromatography combined with femtosecond laser ionization mass spectrometry

Gas chromatography (GC) was combined with femtosecond laser ionization mass spectrometry (fsLIMS) to measure a sample mixture of benzodiazepines (BZDs). To accomplish the fsLIMS, we used the fourth (257 nm, 4.82 eV) and fifth (206 nm, 6.02 eV) harmonic emissions of an ytterbium laser as the ionization laser. The BZD sample mixture was made up of oxazepam, lorazepam, diazepam, temazepam, flunitrazepam, nitrazepam, clonazepam, and alprazolam. When a DB-5 ms capillary column was used for separation, the BZDs were eluted in this respective order. Time-dependent density functional theory was used to calculate the ionization energy of BZDs, and this revealed a range of from 8.34 to 9.12 eV. These values were slightly lower than the two-photon energy of the fourth harmonic emission (9.63 eV), which enhanced the molecular ions while suppressing both the fragment ions and the background signals. Possible fragmentation pathways were examined to explain why molecular ions were missing in both oxazepam and lorazepam even by using fsLIMS.