Rapid and quantitative screening method for 43 benzodiazepines and their metabolites, zolpidem and zopiclone in human plasma by liquid chromatography/mass spectrometry with a small particle column

Benzodiazepines and their pharmacologically related drugs, zolpidem and zopiclone are widely prescribed as safe drugs, but these drugs are also abused in cases of crime, suicide and drug-facilitated sexual assault. We developed a rapid and quantitative screening method for 43 benzodiazepines, their metabolites, zolpidem and zopiclone in human plasma by liquid chromatography/mass spectrometry with a small particle column. All drugs were successfully separated within 12 min using combined scan and selected ion recording (SIR) mode. The calibration curves of most drugs were linear in the concentration range 0.5–250 ng/mL with correlation coefficients exceeding 0.99. Within-day precisions (RSD, %) of this method were 1.8–15.6% (10 ng/mL) and 0.6–10.1% (100 ng/mL) and between-day precisions (RSD, %) were 1.6–16.9% (10 ng/mL) and 0.6–16.7% (100 ng/mL). The average recoveries were 70.1% (10 ng/mL) and 87.1% (100 ng/mL). The limit of detection ranged from 0.2 to 8.0 ng/mL in 37 drugs and was below 0.2 ng/mL in 6 drugs. The established method is sensitive and rapid, thus it should be useful in forensic and clinical toxicological analyses.