Conflicting hair testing results can have an impact in courts: interpretation of single exposure to zolpidem.

It has been recently (1) published in the journal a study about segmental hair analysis after administration to 20 human volunteers of a single 10 mg dose of zolpidem. None of the volunteers had a history of zolpidem consumption. The drug was detected in all the 0–2 cm segment of hair collected 1 month after exposure with concentrations in the range of 135–555 pg/mg, and a mean measured concentration at 250 pg/mg. In several cases, the consecutive segment (2–4 cm) tested also positive for zolpidem. Although the axial diffusion of a single spot of exposure has been recently addressed (2) and does not compromise the interpretation, the quantitative findings of zolpidem after a single exposure do not fit in with our daily experience. As already mentioned by the Chinese group, there results are markedly different from those reported by Villain et al. (3). In a controlled study sponsored by the French Society of Analytical Toxicology, they found, after administration of the same amount of drug (10 mg) and collection of the hair 1 month after exposure, concentrations in the range of 2–10 pg/mg. To explain this major discrepancy, the recent paper was dealing with sample preparation, hair color (melanin content), metabolic capacity, age, gender, body weight and diffusion from sweat or other secretions. Although this can explain some degrees of variations, it cannot account for a 100 difference between individuals. The distribution for drugs of abuse (opiates, amphetamines or cocaine) among the ethnic population has been demonstrated to vary, but not to such an extent. These recent findings can have legal consequences in Courts. In a case of drug-facilitated crime, the defense of a perpetrator can use the 500 pg/mg threshold to document a single administration of 10 mg of zolpidem. Findings of low picogram per milligram of zolpidem in hair will then be considered as minute traces of drug, with no relation to the assault and there is a major potential risk that the hair findings will be released. This is not acceptable for the victim. To document the earlier finding of our group, I have asked several French experts to share their data from cases involving single exposure to zolpidem in drug-facilitated crimes and have added our recent cases. Although it is not possible to establish the exact amount of zolpidem that was administered, it is consistent with a single tablet (10 mg), as evidenced by the police investigations. In all cases, the method was fully validated or even ISO 17025 accredited. Hair preparation was different according to the laboratories, but all incubated the segmented/pulverized hair in a buffer. All laboratories used LC–MS-MS and the limit of quantitation was between 0.5 and 1.0 pg/mg. The following concentrations were obtained in the hair segment corresponding to the period of the assault (Table I). Six different laboratories measured zolpidem in hair after a single exposure in 49 cases and the drug was found in the range of 0.5–47 pg/mg, with a mean measured value of 11.3 pg/mg. Obviously, these concentrations are far lower than those measured by Cui et al. (1). There is no other controlled study in the scientific literature. However, some scientists over the world have published zolpidem findings in hair after single administration for criminal purposes. In Italy, Salomone et al. (4) measured zolpidem in the hair of a rape case in the low picogram per milligram range. In Australia, Robertson and Staikos (5) detected zolpidem at 30 pg/mg in the hair of a victim. In Korea, Kim et al. (6) also detected zolpidem at very low concentrations. In Sweden, Kronstrand (7) measured 4 pg/mg of zolpidem in the hair of a victim of kidnapping. Typically from the literature (8, 9), concentrations of zolpidem in hair in the range of 400 pg/mg or over correspond to drug abusers or long-term users. Zolpidem (Stilnox in France, Ambien in the USA) is an imidazopyridine derivative used since 1986 in Europe and since 1993 in the USA as a hypnotic agent. The purported enhancement of sexuality, coupled with a possible abrupt coma-inducing effect, ease of administration in spiked drinks (particularly coffee) and potential amnesia has resulted in the use of zolpidem as an assault-related drug. Zolpidem is also attractive to rapists as it is readily available in pharmacies. Epidemiological studies in France (10, 11) have indicated that the prevalence of zolpidem is high in drug-facilitated crimes. Given the risk of misinterpretation of the data of Cui et al. (1), the authors see no reason to support the findings of the Chinese group but expect and recommend further studies and improvements in the interpretation of the data to contribute to document drug-facilitated crimes. The use of a 1–20 pg/mg range of zolpidem to account for a single dose exposure is not only based on the literature data (referred to by the authors of the letter) but also based on the practical experience gained from hundreds of cases in multiple laboratories where zolpidem detection and reporting have been successfully applied for many years. Finally, the Society of Hair Testing (12) has indicated in its last guidelines that concentrations in the low picogram per milligram range are expected in drug-facilitated crime cases, confirming our earlier publications. The publication of Cui et al. (1) of very high concentrations of zolpidem after a single dose in comparison with the first set of data from Villain et al. (3) has led to a general uncertainty with respect to the value of hair analysis for drugs. However, it seems that these findings concern mainly a specific group of volunteers. After 10 years of successful experience, hair analysis continues to be a suitable tool in documenting drugfacilitated crime cases.