Quantification of lorazepam and lormetazepam in human breast milk using GC-MS in the negative chemical ionization mode

Lormetazepam (Loramet®) is a benzodiazepine mainly used as an hypnotic to treat insomnia. Lorazepam (Temesta®) is used as an anxiolytic, tranquilizer, sedative, and anticonvulsant, and it is the major metabolite of lormetazepam. In this study, we designed a method to simultaneously detect and quantify these substances in human breast milk. Solid-phase extraction of 2 mL of milk was followed by derivatization with a trimethylsilyl reagent. Separation and detection was performed using gas chromatography coupled to mass spectrometry in the negative chemical ionization mode. Calibration curves were linear in the ranges of 10-200 and 1-20 ng/mL for lorazepam and lormetazepam, respectively. Limits of detection were estimated at 0.016 ng/mL for lormetazepam and 0.100 ng/mL for lorazepam. Our method was applied to real case samples from a woman receiving both benzodiazepines. Lorazepam concentrations varied from 55.3 to 123.1 ng/mL, and lormetazepam concentrations varied from 1.7 to 7.3 ng/mL.