Hair analysis for doxylamine

Doxylamine is one of the first effective antihistamine agents to have been discovered. The compound is also used as a sedative night-time cold and allergy relief drug and for its antiemetic effects. The first case involving sedation linked to the use of doxylamine as a drug-facilitated crime and subsequent impairment of a 21-year-old female victim is reported. Due to the long delay between the alleged crime and clinical examination, collection of blood or urine was of little value. Hence, the laboratory developed an original approach based on hair testing by liquid chromatography–tandem mass spectrometry. A lock of hair from the victim was collected 5 weeks after the suspected administration. After cutting into small pieces, about 20 mg of hair was incubated overnight in a phosphate buffer (pH 8.4). The aqueous phase was extracted with 5 ml of a mixture of methylene chloride/diethyl ether (80/20), in presence of haloperidol-d₄, used as internal standard (IS). The hair extract was separated on an XTerra MS C18 column using a gradient of acetonitrile and formate buffer. Detection was based on two daughter ions: transitions m/z 271.3–182.1 and 167.0 and m/z 380.2–169.2 for doxylamine and the IS, respectively. In the hair of the woman, doxylamine was detected in the proximal segment (0–3 cm) at a concentration of 37 pg/mg. The concentration was compared with those obtained after a single dose and after daily dose administration. In the hair of four subjects receiving a single 15-mg dose and collected 4 weeks later, doxylamine was detected in the proximal segment at 18–52 pg/mg. After daily 15-mg doses for at least 4 months, the hair concentrations of three subjects under doxylamine therapy were 840–2050 pg/mg.