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At least 19 recordsLinked to original sources
PubMed1991

Determination of diazepam and nordazepam in milk and plasma in the presence of oxazepam and temazepam.

For studies on the excretion of drugs into milk a sensitive high-performance liquid chromatographic assay was developed to quantitate diazepam and nordazepam in the milk and plasma of humans and rabbits in the presence of their major metabolites, oxazepam and temazepam. Flurazepam was used as an internal standard. The assay involves extractions with diethyl ether and an additional acid clean-up step. Chromatographic separation was achieved by a LiChrospher 60 RP-select B (5 microns) column and KH2PO4- acetonitrile (69:31, v/v) adjusted to pH 2.80 as a mobile phase. The same extraction and chromatographic conditions were suited to both types of samples, milk and plasma. The limits of determination using ultraviolet detection at 241 nm was for diazepam 20 ng/ml and for nordazepam 15 ng/ml. The absolute recoveries of diazepam, nordazepam and flurazepam in human milk were 84, 86 and 92% and in human plasma 97, 89 and 94%, respectively. The within- and between-day accuracy and precision for diazepam and nordazepam in milk and plasma at all concentrations tested (20-1500 ng/ml) were better than 8%. The high fat content which occurs in rabbit milk presented no limitation for the extraction of lipophilic diazepam: the method was successfully used to monitor milk and plasma concentrations of diazepam and nordazepam in lactating New Zealand White rabbits during 26-h infusions of diazepam (1.4 mg/h).

Chromatography, High Pressure Liquid↗
PubMed1992

Studies on the excretion of diazepam and nordazepam into milk for the prediction of milk-to-plasma drug concentration ratios.

The influence of varying protein and fat content in milk of New Zealand White rabbits on the milk-to-plasma drug concentration (M/P) ratio of diazepam was studied. At various time points after littering, a bolus dose (1.5 mg/kg) followed by a 26-hr infusion (1.8 mg/h) of diazepam was administered to freely moving rabbits via a jugular vein catheter. Milk and blood samples were collected to allow characterization of milk composition and quantitative determination of diazepam and nordazepam in milk and plasma. At steady state diazepam showed M/P ratios between 3.7 and 9.5, whereas nordazepam showed ratios between 2.1 and 4.3, respectively. The relative importance of milk protein binding and milk-fat partitioning for the excretion of a drug into milk depended on the drug's affinity to milk fat. A stepwise multiple regression analysis suggested that observed M/P ratios of diazepam could be explained by considering the fat content of milk alone. Nordazepam with a lower solubility in milk fat showed M/P ratios which could be best explained by considering protein and fat concentrations together. Using the data from the infusion studies, two recently published diffusional models to predict M/P ratios were evaluated. Neither model could accurately predict the M/P ratios of diazepam and nordazepam observed in rabbits. However, after extending the model described by Atkinson and Begg to take the actually measured partitioning between skim milk and milk fat into account, a great improvement in the predictive power for observed M/P ratios occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Cytochrome P450IIIA enzymes in rat liver microsomes: involvement in C3-hydroxylation of diazepam and nordazepam but not N-dealkylation of diazepam and temazepam.

Microsomes prepared from livers of male and female rats of nine inbred and outbred strains and of male Sprague-Dawley rats pretreated with monooxygenase-inducing agents were used to study N-dealkylation of diazepam and temazepam and C3-hydroxylation of diazepam and nordazepam. Both C3-hydroxylation reactions were more rapid in male than in female liver preparations, but this gender-dependent pattern was not seen with the N-dealkylation reactions. These results indicate the lack of identity of the monooxygenases responsible for the two kinds of reaction and suggest that male-specific enzyme(s) are responsible for the C3-hydroxylations. Induction studies were undertaken to further define these enzymes. To do this, liver microsomes prepared from male Sprague-Dawley rats pretreated with a variety of agents known to have different monooxygenase induction effects were used. With triacetyloleandomycin, dexamethasone, and phenobarbital pretreatment, the specific activities of the C3-hydroxylation reactions were selectively elevated over corresponding control values. These particular xenobiotics are known to enhance the abundance of cytochrome P450IIIA family enzymes, and our results strongly suggest the involvement of these enzymes in the benzodiazepine B ring monooxygenations. Formation of temazepam was also shown to be inhibited by triacetyloleandomycin. This effect was demonstrated to be equal in both saline-treated and dexamethasone-treated male Sprague-Dawley rat liver microsomes, with the antibiotic present either with diazepam throughout the entire incubation period or initially with NADPH in a preincubation mix for 15 min, following which C3-hydroxylation was initiated by the addition of diazepam. These results confirm the uniformity of the involvement of cytochrome P450IIIA family enzymes in diazepam C3-hydroxylation in untreated and inducer-treated rat liver microsomes. Recent studies with human and rabbit liver microsomal preparations have shown that orthologues of these enzymes also catalyze an equivalent hydroxylation in the B ring of midazolam. These findings, considered with the present results showing that the adjacent methyl N-substituent (absent in nordazepam but present in diazepam) did not affect the selectivity of these enzymes for the C3-hydroxylation reaction, suggest that neither steric nor electronic factors markedly influence catalysis of this monooxygenation by these enzymes.

Animals↗
PubMed2006

A sensitive and selective method for the detection of diazepam and its main metabolites in urine by gas chromatography-tandem mass spectrometry.

A gas chromatography-tandem mass spectrometry method for detection of diazepam, nordazepam and oxazepam is presented. The method associates electron capture ionization and multiple reaction monitoring (MRM). No derivatization is performed; oxazepam undergoes thermal degradation during chromatographic injection and is thus quantified via its decomposition product. The negative molecular ions are so stable that they do not dissociate when collision is performed under "classical" conditions (i.e. with argon as collision gas). With xenon as collision gas, the energy transfer is sufficient to provide two product ions for diazepam and nordazepam and one product ion for the decomposition product of oxazepam. The sample preparation part involves liquid/liquid extraction with TOXI-TUBES A extraction tubes; it provides recovery yields between 68 and 95%, depending of the benzodiazepine considered, with coefficients of variation below 6% for 10 samples. The applicability of the method was demonstrated on urine extracts. From 1 mL of urine, the method provides quantitation limits of 0.15 ng/mL for diazepam, 1.0 ng/mL for nordazepam and 1.5 ng/mL for oxazepam. Mechanisms of dissociation of M*(-) ions of benzodiazepines are suggested.

Benzodiazepinones↗
PubMed1992

Benzodiazepine metabolism in ethanol-treated male rats: use of pair-fed and age-matched controls.

The effects of chronic moderate (15%) ethanol consumption and ageing on rat hepatic cytochrome P450 monooxygenase activities were examined using diazepam, nordazepam, d-benzphetamine, erythromycin, ethylmorphine and nitrosodimethylamine (NDMA) as substrates. In addition, the effects of moderate ethanol alone on the oxidation of metoprolol, morphine and temazepam were examined. Cytochrome P450 specific content increased significantly only in the 6-week ethanol-treated rats, and no changes in percentage liver to body weights were apparent in any of the ethanol-treated animals compared with pair-fed controls. Only cytochrome P450IIIA enzyme activities displayed age-related decreases, these being identified in the pair-fed animals. C3-hydroxylation of diazepam and nordazepam (36% of controls) and N-demethylation of erythromycin and ethylmorphine (58% and 64% of controls) were decreased in 6-week ethanol-treated animals, these effects being less pronounced in the 12, 24 and 48-week ethanol-treated groups. The decrease seen for diazepam and d-benzphetamine N-demethylation caused by ethanol consumption was approximately 80% of control groups for the duration of the treatment. NDMA and morphine N-demethylations were increased to 120% of control activities and metoprolol alpha-hydroxylase was increased to 140% of control activities at 6 weeks, whilst metoprolol O-demethylase activity remained unaltered. NDMA N-demethylase activity showed a two-fold induction at 24 and 48 weeks of ethanol treatment, compared with corresponding pair-fed control groups. These results support previous findings from this laboratory showing that the same or similar P450IIIA family isozymes are involved in the C3-hydroxylation of diazepam and nordazepam.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1994

[Electroencephalographic demonstration of central nervous system effects of different premedication regimens].

INTRODUCTION: For many years, the main goal of premedication was prevention of the dangerous side effects sometimes encountered in anesthetics with anticholinergics, antiemetic antihistaminics, and opioids. Because the rules were always preoperative fasting, premedication was administered i.m. Thus, the onset of action was within 15-30 min from administration. In recent years, with the introduction of newer anesthetics with fewer side effects, anxiolysis became the main aim in premedication. Moreover, the oral route became popular since it obviously did not increase the acidity or volume of the gastric content. However, the uptake and thus onset of action of orally administered drugs may take longer and can differ considerably between individual patients. Therefore, the optimum interval between administration and induction of anesthesia remains controversial. The present study was carried out to examine the time course of drug action and the effects of different premedication regimens on the electroencephalogram (EEG). PATIENTS AND METHODS: After obtaining informed consent, in 38 unselected adult patients (ASA I and II, < 65 years) scheduled for elective surgery, the EEG was recorded continuously before and after premedication. The patients were randomly assigned to four groups: M: midazolam, 0.2 mg/kg BW orally; N: nordazepam, 0.2 mg/kg BW orally; AP: atropine, 0.5 mg, plus promethazine, 50 mg i.m.; APP: atropine, 0.5 mg, plus promethazine, 50 mg, plus pethidine, 0.7 mg/kg BW i.m. The EEG was recorded for a reference period of 10 min before and a study period of 30 min after premedication. Automated EEG processing was performed with CATEEM (computer-aided topographical electroencephalometry). Surface electrodes were placed according to the 10-20 system. Date were collected via an amplifier (resistance 10 M omega) and a digitalization unit (filter 0.2-35 Hz, sampling rate 512 Hz, 12 bit A/D convertor). The original EEG signals were used in an interpolation algorythm to produce an additional 82 virtual recording points, allowing for high topographical resolution. After spectral analysis (fast Fourier transformation), the different frequency ranges of the EEG power spectrum are displayed in different colors. The screen displays the on-line map with color-based topographical power distribution. In order to achieve a pharmacodynamic time profile, the study period was subdivided into three periods of 10 min each. For clinical evaluation of vigilance, a 6-grade scoring system was used 1 = awake, 6 = not arousable). RESULTS: All data are presented with respect to reference period. The power density of each frequency range for each electrode is integrated over the selected period and mean values are shown. Changes in power density with time are expressed as percentage change from reference period. Biometrical data showed no significant differences between groups. The median vigilance score 30 min after premedication (end of study period) was 4 in groups M, AP, and APP, and 3 in group N. In both benzodiazepine groups, a distinct increase in power density was found in the beta-bands, while in groups AP and APP the increase was most pronounced in the delta and theta bands. In group M, there was a linear increase in beta 1 power up to 310%, while in the beta 2 range there was a 170% maximum within the second period of 10 min. In group N, there was a similar course with a lower increase in beta 1 (220%) and beta 2 (130%). Increases in both beta-bands were most pronounced with frontal electrodes. While group M showed an increase in delta power (150%), together with moderate suppression in alpha (alpha 1 50%, alpha 2 40%), nordazepam caused only a slight increase in delta (124%) and a distinct increase in alpha 2 to 150%, predominantly in the frontal areas. Group APP showed a linear increase in both delta up to 210% and theta power to 190%. (ABSTRACT TRUNCATED)

Adult↗
PubMed2005

Fast, simple, and validated gas chromatographic-mass spectrometric assay for quantification of drugs relevant to diagnosis of brain death in human blood plasma samples.

In addition to total anamnesis, one of the important aspects in diagnosis of brain death is the exclusion of effective plasma concentrations of drugs that might mimic brain death. A minimum consensus for toxicological analysis in this context includes relevant analytes (thiopental, pentobarbital, methohexital, phenobarbital, diazepam, nordazepam, and midazolam) and proposes limits of quantification. Propofol is another relevant drug. After liquid-liquid extraction of 200 microL of plasma using 50 microL of a solution of deuterated internal standards in butyl acetate and 50 microL of butyl acetate, 2 microL of the organic phase was analyzed by gas chromatography-mass spectrometry using selected-ion monitoring mode. Validation included the parameters selectivity, calibration model, precision and accuracy, and extraction efficiency. Accuracy and precision data obtained using 6-point and 1-point calibration were compared. The abovementioned analytes were separated within 10 minutes and sensitively detected. No interfering peaks were observed in blank samples from 10 different sources. The linearity ranges were 0.5-6 mg/L for propofol, 0.25-10 mg/L for pentobarbital and thiopental, 0.125-10 mg/L for methohexital, 2.5-50 mg/L for phenobarbital, 0.05-2.5 mg/L for diazepam and nordazepam, and 0.01-0.5 mg/L for midazolam. Extraction efficiency ranged from 85% to 111%. The acceptance criterion for accuracy and precision (99% confidence interval of measured mean within +/-50% of target value) was fulfilled for all analytes, even with 1-point calibration using a calibrator close to the center of the linearity range. The assay was applied to analysis of real brain death cases. In conclusion, the described assay allowed fast and reliable determination of analytes relevant to diagnosis of brain death, and 1-point calibration kept the workload low.

Brain Death↗
PubMedDate not supplied

Pilot investigation of thyrotropin-releasing hormone-induced thyrotropin and prolactin release in anxious patients treated with diazepam.

Benzodiazepines have been reported to inhibit thyrotropin (TSH) and prolactin (PRL) secretion in response to stressful and pharmacologic stimuli in experimental animals. The current study investigates basal and thyrotropin-releasing hormone (TRH)-stimulated TSH and PRL release in anxious patients treated with diazepam. Six hospitalized patients having generalized anxiety or adjustment disorder with anxious mood (DSM III-R criteria) were treated during 1 week with diazepam (mean daily dose 33.3 mg). TRH testing was performed comparatively before and after 7 days of diazepam administration (with 250 micrograms protirelin and blood sampling at 15-min intervals over 60 min). Steady-state plasma levels of diazepam and its metabolite nordazepam (desmethyldiazepam) were determined by high-performance liquid chromatography. After 7 days of diazepam treatment, basal plasma levels of TSH and PRL were not affected compared with pretreatment values. Similarly, the time-course of TRH-induced TSH release was not modified by the treatment. By contrast, there was a trend to decrease in the TRH-induced PRL release, and the decrease in the PRL response to TRH on day 7 was significantly correlated with plasma nordazepam concentrations (rs = 0.943, p = 0.02). These preliminary results suggest that benzodiazepines, at therapeutic doses for the treatment of anxiety, may alter TRH-induced PRL release in humans.

Adolescent↗
PubMed1999

Prolonged sedation requiring mechanical ventilation and continuous flumazenil infusion after routine doses of clorazepam for alcohol withdrawal syndrome.

We report the cases of two patients who developed prolonged sedation after routine doses of clorazepam for alcohol withdrawal syndrome. They required prolonged mechanical ventilation (10 days for both patients) followed by continuous flumazenil infusion (16 days for one patient and 3 days for the other) to avoid reintubation. In the two patients, nordazepam accumulation (main active metabolite of clorazepam) was demonstrated as the cause of the coma. This accumulation could be attributed, in one case, to impaired hepatic cytochrome P 450 3A4 activity. Caution is required when prescribing benzodiazepines to alcoholic patients and the use of benzodiazepine which do not undergo hepatic oxidation by cytochrome P 450 such as oxazepam or lorazepam is suggested.

Aged↗
PubMed2006

Medicolegal aspects of tetrazepam metabolism.

The benzodiazepine tetrazepam is primarily muscle relaxant with comparably lower central sedating effects and is therefore commonly prescribed for muscle spasms of different origins. To evaluate tetrazepam metabolism, a study was conducted with ten healthy volunteers. Blood and urine samples were regularly collected after the intake of 50 mg tetrazepam. Toxicological analyses revealed that tetrazepam is also metabolized to diazepam and further to nordazepam, which has not yet been reported. Tetrazepam and diazepam could be detected in urine samples at least 72 h after intake, the diazepam concentration being 33% (+/-14% SD), on average, of the tetrazepam concentration. On the basis of three case histories, the importance of the detection of these newly described metabolites is shown as necessary to prevent false accusations and potential negative legal consequences for examined persons.

Adult↗
PubMed2000

Fatal intoxication with melperone.

Melperone is judged to be a safe neuroleptic drug. Until now there has been no report of a melperone fatality, though it has been used in suicide attempts. We report on a case of a 36-year-old woman where no cause of death could be established at autopsy. Criminological investigation pointed to a homicide by poisoning but also the possibility of a suicide had to be taken in account. The toxicological analysis of blood, cerebral spinal fluid and urine revealed extremely high concentrations of melperone which had never been reported before. Furthermore, diazepam, nordazepam and carbamazepine were detected. To our knowledge, this case is the first melperone fatality. Possible interactions with diazepam and carbamazepine are discussed.

Adult↗
PubMedDate not supplied

[Possibilities for toxicologic evidence in adipocere formation and postmortem interval of several years].

It is reported on a 31-year-old man, whose dead body was found together with numerous packets of poisons and medicaments in a forest after a post-mortem period of nearly 3 years. Despite advanced skeletization and complete transformation of the still existing residual soft tissues to adipocere, highly toxic concentrations of two heavy metals (cadmium: 0.30 mg/kg; thallium: 0.91 mg/kg) and minor levels of three organic substances (phenobarbitone: 0.32 mg/kg; nordazepam: 0.14 mg/kg; salicylic acid: 0.04 mg/kg) were detected in adipoceratous samples. Even if it is not possible to derive similar blood levels from post-mortem values, the cause and manner of death (suicidal intoxication) could be clarified with the necessary degree of certainty. Few comparable literature reports either deal with exhumations or non-toxic concentrations of substances in morphologically better preserved adipoceratous bodies. Our case demonstrates that toxicological analyses may contribute to the clarification of the cause of death even if advanced adipocere formation with a longer post-mortem interval is present.

Adipose Tissue↗
PubMed2004

Screening, library-assisted identification and validated quantification of 23 benzodiazepines, flumazenil, zaleplone, zolpidem and zopiclone in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization.

A liquid chromatographic/mass spectrometric assay with atmospheric pressure chemical ionization (LC/APCI-MS) is presented for fast and reliable screening and identification and also for precise and sensitive quantification in plasma of the 23 benzodiazepines alprazolam, bromazepam, brotizolam, camazepam, chlordiazepoxide, clobazam, clonazepam, diazepam, flunitrazepam, flurazepam, desalkylflurazepam, lorazepam, lormetazepam, medazepam, metaclazepam, midazolam, nitrazepam, nordazepam, oxazepam, prazepam, temazepam and tetrazepam, triazolam, their antagonist flumazenil and the benzodiazepine BZ1 (omega 1) receptor agonists zaleplone, zolpidem and zopiclone. It allows confirmation of the diagnosis of an overdose situation and monitoring of psychiatric patients' compliance. The analytes were isolated from plasma using liquid-liquid extraction and were separated on a Merck LiChroCART column with Superspher 60 RP Select B as the stationary phase. Gradient elution was performed using aqueous ammonium formate and acetonitrile. After screening and identification in the scan mode using the authors' LC/MS library, the analytes were quantified in the selected-ion monitoring mode. The quantification assay was fully validated. It was found to be selective proved to be linear from sub-therapeutic to over therapeutic concentrations for all analytes, except bromazepam. The corresponding reference levels the assay's accuracy and precision data for all studied substances are listed. The accuracy and precision data were within the required limits with the exception of those for bromazepam. The analytes were stable in frozen plasma for at least 1 month. The validated assay was successfully applied to several authentic plasma samples from patients treated or intoxicated with various benzodiazepines or with zaleplone, zolpidem or zopiclone. It has proven to be appropriate for the isolation, separation, screening, identification and quantification of the drugs mentioned above in plasma for clinical toxicology, e.g. in cases of poisoning, and forensic toxicology, e.g. in cases of driving under the influence of drugs.

Anti-Anxiety Agents↗
PubMed2002

Fatal accident caused by isoflurane abuse.

A fatal accident after isoflurane abuse is presented in this report. A hospital employee was found dead in the operating area with a plastic bag over his head. In his locker an almost empty bottle of isoflurane was found. Autopsy revealed signs of asphyxiation and toxicological examination revealed nordazepam and isoflurane in non-toxic concentrations in the blood. Quantification of the anaesthetic was also carried out in urine, gastric contents, liver, kidney and brain samples, and in addition, oxazepam, prothipendyl and metabolites of midazolam and prothipendyl were found in the urine. Although the drug problems of the deceased were known before, no efforts had been made to restrict access to these drugs.

Accidents↗
PubMed2005

Quantification of benzodiazepines in whole blood and serum.

A high-performance liquid chromatography method for the determination of benzodiazepines and their metabolites in whole blood and serum using mass spectrometry (MS) and photodiode array (PDA) detection is presented. The combination of both detection types can complement each other and provides extensive case relevant data. The limits of quantification (LOQ) with the MS detection lie between 2 and 3 microg/l for the following benzodiazepines or metabolites: 7-amino-flunitrazepam, alprazolam, desalkyl-flurazepam, desmethyl-flunitrazepam, diazepam, flunitrazepam, flurazepam, alpha-hydroxy-midazolam, lorazepam, midazolam, nitrazepam, nordazepam and oxazepam, respectively 5 microg/l for lormetazepam and 6 microg/l for bromazepam. The LOQ of clobazam determined with the PDA detector is 10 microg/l. A convenient approach for determining the measurement uncertainty of the presented method--applicable also for other methods in an accreditation process--is presented. At low concentrations (<10 microg/l), measurement uncertainty was estimated to be about 50%, and at concentrations >180 microg/l, it was estimated to be about 15%. One hundred and twenty-eight case data acquired over 1 year are summarised.

Anti-Anxiety Agents↗
PubMed1987

Identification and differentiation of benzodiazepines and their metabolites in urine by computerized gas chromatography-mass spectrometry.

A method for the identification and differentiation of the following benzodiazepines and their metabolites in urine after acid hydrolysis and acetylation is described: bromazepam, camazepam, chlordiazepoxide, clobazam, clonazepam, clorazepate, clotiazepam, cloxazolam, delorazepam, diazepam, ethylloflazepate, flunitrazepam, flurazepam, halazepam, ketazolam, loprazolam, lorazepam, lormetazepam, medazepam, metaclazepam, midazolam, nitrazepam, nordazepam, oxazepam, oxazolam, prazepam, quazepam, temazepam and tetrazepam. The acetylated extract was analysed by computerized gas chromatography-mass spectrometry. An on-line computer allowed rapid detection using ion chromatography with ions m/z 205, 211, 230, 241, 245, 249, 312 and 333. The identity of positive signals in the reconstructed ion chromatogram was confirmed by a comparison of the stored full mass spectra with reference spectra. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (on OV-101) are documented.

Acetylation↗
PubMedDate not supplied

Solid-phase extraction of 1,4-benzodiazepines from biological fluids.

The solid-phase extraction (SPE) of seven 1,4-benzodiazepines (oxazepam, diazepam, temazepam, nordazepam, brotizolam, adinazolam and midazolam) using prazepam as internal standard was investigated. The 1,4-benzodiazepines were recovered from an aqueous buffer of suitable pH, using C18 Sep-Pak cartridges and mixtures of methanol-water as elution solvent. The recovery of oxazepam using different sorbent materials (C2, C8, C18, cyanopropyl, phenyl and cyclohexyl Bond-Elut) was also examined as a function of pH and the composition of the elution solvent. The SPE of oxazepam was investigated using spiked urine samples and the C2 cartridge gave rise to the cleanest urine extracts. The recoveries of the other 1,4-benzodiazepines from spiked urine and plasma samples using the C2 cartridge was then found to be higher than 90%, without any interference from endogenous compounds of the samples. Finally, the influence of other factors such as drug concentration, sample volume and the number of times the SPE cartridge had been used was also examined.

Benzodiazepines↗
PubMed2005

Hair analysis by liquid chromatography-tandem mass spectrometry in toxicological investigation of drug-facilitated crimes: report of 128 cases over the period June 2003-May 2004 in metropolitan Paris.

In recent years, reports of drug-facilitated crimes (DFC) have been increasing. The drugs involved are sometimes difficult to detect, because of their low dosages and the long time ellapsed between alleged DFC and blood and urine sampling. In order to detect benzodiazepines and benzodiazepine-like hypnotics, we developed an approach for hair analysis by liquid chromatography-tandem mass spectrometry using a triple stage quadrupole with an electrospray ionization (LC-ESI-MS/MS). Separation was performed on an Uptisphere ODB C18 column using a gradient of 2mM formate buffer and acetonitrile. For the 23 compounds studied, detection limits are lower than 2 pg/mg, but a specific extraction procedure is needed for 7-amino metabolites. Over a 1-year period within the city limits of Paris and three suburbs, we tested blood and urine from victims of sexual assaults, robbery and battery in which psychoactive substances were suspected of being involved. Hair was collected 4-8 weeks after the alleged DFC. Over the 128 cases studied, results of simultaneous analysis of blood, urine, and hair allowed us to conclude that 23 cases were real DFC. In 18 cases, no conclusion was possible since no hair was sampled and/or results were negative. In 56 cases, victims were previously using narcotics, cannabis, and/or a prescribed drug, according to the compounds detected in hair strands. Thirty-one cases were not DFC cases. This study indicates that the prevalence of zolpidem and clonazepam is high, followed by bromazepam, nordazepam, and midazolam. Others benzodiazepines and analogs are rare. LC-ESI-MS/MS is a good tool for toxicological investigations of DFC. Testing blood, urine, and hair by this technique may reveal drug presence, even if it was administered at a single therapeutic dose. That may be helpful to prosecute perpretators or to exclude a drug-facilitated crime.

Adolescent↗