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V Cirimele

Publications and source records attributed to V Cirimele.

At least 19 recordsLinked to original sources
PubMed2005

Evidence of addiction by anesthesiologists as documented by hair analysis.

Chemical dependency is a disease that can affect all professions. Among the health care professionals, anesthesiologists represent a specific group. Numerous factors have been proposed to explain the high incidence of drug abuse among anesthesiologists. These include: easy access to potent drugs, particularly narcotics, highly addictive potential of agents with which they are in contact, and easy diversion of these agents since only small doses will initially provide an effect desired by the abuser. Opioids are the drugs of choice for anesthesiologists, and among them fentanyl and sufentanil are the most commonly used. Alcohol is mostly abused by older anesthesiologists. Propofol, ketamine, thiopental and midazolam are also abused. In fact, all but quaternary ammonium drugs can be observed. Signs and symptoms of addiction in the hospital workplace include: unusual changes in behavior, desire to work alone, refusal of lunch relief or breaks, volunteer for extra cases, call, come in early and leave late, frequent restroom breaks, weight loss and pale skin, malpractice, behind on charts .... Toxicological investigations are difficult, as the drugs of interest are difficult to test for. In most cases, half-lives of the compounds are short, and the circulating concentrations weak. It is, therefore, necessary to develop tandem mass spectrometry procedures to satisfy the criteria of identification and quantitation. In most cases, blood and/or urine analyses are not useful to document impairment, as these specimens are collected at inadequate moments. Hair analysis appears, therefore, as the unique choice to evidence chronic exposure. Depending the length of the hair shaft, it is possible to establish an historical record, associated to the pattern of drug use, considering a growth rate of about 1cm/month. An original procedure was developed to test for fentanyl derivatives. After decontamination with methylene chloride, drugs are extracted from the hair by liquid/liquid extraction after incubation in pH 8.4 phosphate buffer. Fentanyl derivatives are analyzed by GC-MS/MS. The following cases are included in this paper: Case 1: 50-year-old anesthetist, positive for fentanyl (644 pg/mg); Case 2: 42-year-old anesthetist, positive for fentanyl (101 pg/mg) and sufentanil (2 pg/mg); Case 3: 40-year-old anesthetist, positive for codeine (210 pg/mg), alfentanil (30 pg/mg) and midazolam (160 pg/mg); Case 4: 46-year-old nurse, found dead, positive for alfentanil (2 pg/mg) and fentanyl (8 pg/mg). In these cases, the combination of an alternative specimen (hair) and hyphenated analytical techniques (tandem mass spectrometry) appears to be a pre-requisite.

Adult↗
PubMed2005

Dioxins and furans determination in postmortem blood by gas chromatography--high-resolution mass spectrometry.

Dioxins and related compounds (furans) are persistent environmental contaminants that cause adverse biological effects. Their influence on humans is still unclear, except for accidental high-dose exposure. However, chronic exposure to these compounds seems to be involved in cancer, endocrine disruption, and neurobehavioral effects. For several years, a large concern about the potential health risks of dioxins is emerging in Europe and United States. Dioxin levels in biological specimens are extremely low and require very sensitive and specific methods of analysis. In this study, gas chromatography coupled to high-resolution mass spectrometry was used to evaluate dioxin body burden of two women deceased from generalized cancer. Fat fraction of blood specimens was obtained after precipitation with ethanol and extraction of both liquid and solid phases spiked with labeled 13C12-dioxin analogues. Organic phases were grouped, washed, and evaporated to weigh the lipid content. Lipids were dissolved in hexane, hydrolyzed with concentrated sulfuric acid, and discarded during water washes. Dioxins purification was achieved using three successive columns: silica, alumina/sodium sulfate, and carbon/Celite. Finally, the toluene eluent was evaporated and the extract injected in the analytical system. After chromatographic separation, detection was achieved in single ion monitoring mode using a high-resolution mass spectrometer operating in electron impact ionization mode (40 eV, minimal resolution of 10,000). Dioxin levels were expressed in pg TEQ/g of fat as defined by the World Health Organization. Quantification limits for each dioxin congener ranged from 2.5 to 12.0 pg/g fat with a relative extraction recovery always higher than 60%. Dioxin concentrations in the blood of the two deceased women were 35.0 and 42.7 pg TEQ/g fat, respectively. These concentrations are largely lower than those observed after accidental releases, but in the range of those observed in the general European population. Therefore, it was not possible to correlate dioxin body burden of the two women as a potential contributor of their cancer pathology. Nevertheless, knowledge of dioxin body burden in the French population would be of interest for an accurate interpretation of these results.

Aged↗
PubMed2004

Evaluation of the One-Step ELISA kit for the detection of buprenorphine in urine, blood, and hair specimens.

A solid-phase enzyme immunoassay involving microtiter plates was recently proposed by International Diagnostic Systems corporation (IDS) to screen for buprenorphine in human serum. The performance of the kit led us to investigate its applicability in other biological matrices such as urine or blood, and also hair specimens. Low concentrations of buprenorphine were detected with the ELISA test and confirmed by HPLC/MS (buprenorphine concentrations measured by HPLC/MS: 0.3 ng/mL in urine, 0.2 ng/mL in blood, and 40 pg/mg in hair). The intra-assay precision values were 8.7% at 1 ng/mL of urine (n = 8), 11.5% at 2 ng/mL in serum (n = 8), and 11.5% at 250 pg/mg of hair (n = 8), respectively. The immunoassay had no cross-reactivity with dihydrocodeine, ethylmorphine, 6-monoacetylmorphine, pholcodine, propoxyphene, dextromoramide, dextrometorphan at 1 and 10 mg/L, or codeine, morphine, methadone, and its metabolite EDDP. A 1% cross-reactivity was measured for a norbuprenorphine concentration of 50 ng/mL. Finally, the immunoassay was validated by comparing authentic specimens results with those of a validated HPLC/MS method. From the 136 urine samples tested, 93 were positive (68.4%) after the ELISA screening test (cutoff: 0.5 ng/mL) and confirmed by HPLC/MS (buprenorphine concentrations: 0.3-2036 ng/mL). From the 108 blood or serum samples screened, 27 were positive (25%) after the ELISA test with a cutoff value of 0.5 ng/mL (buprenorphine concentrations: 0.2-13.3 ng/mL). Eighteen hair specimens were positive (72%) after the screening (cutoff: 10 pg/mg) and confirmed by LC/MS (buprenorphine concentrations: 40-360 pg/mg). The ELISA method produced false positive results in less than 21% of the cases, but no false negative results were observed with the immunological test. Four potential adulterants (hypochloride 50 mL/L, sodium nitrite 50 g/L, liquid soap 50 mL/L, and sodium chloride 50 g/L) that were added to 10 positive urine specimens (buprenorphine concentrations in the range 5.3-15.6 ng/mL), did not cause a false negative response by the immunoassay.

Buprenorphine↗
PubMed2003

Testing for kavain in human hair using gas chromatography-tandem mass spectrometry.

A sensitive, specific and reproducible method for the quantitative determination of kavain in human hair has been developed. The sample preparation involved a decontamination step of the hair with methylene chloride. The hair sample (about 50 mg) was incubated in 1 ml of methanol for 1 h, in an ultrasonic bath, in presence of 20 ng of methaqualone-d7 used as internal standard. The methanolic solution was evaporated to dryness, and the residue reconstituted by adding 30 microl of methanol. A 2 microl aliquot of the extract was injected onto the column (Optima5-MS capillary column, 5% phenyl-95% methylsiloxane, 30 m x 0.25 mm i.d. x 0.25 mm film thickness) of a Hewlett-Packard (Palo Alto, CA) gas chromatograph (5890). Kavain was detected by its parent ion at m/z 230 and daughter ions at m/z 111 and 202 through a Finnigan TSQ 700 MS/MS system. The assay was capable of detecting 30 pg/mg of kavain (limit of detection (LOD)). Linearity was observed for kavain concentrations ranging from 100 to 2000 pg/mg with a correlation coefficient of 0.998. Intra-day precision at 400 pg/mg was 13.7%. The analysis of a segment of hair, obtained from an occasional consumer, revealed the presence of kavain at the concentration of 418 pg/mg. A higher concentration (1708 pg/mg) was detected in the corresponding pubic hair.

Calibration↗
PubMed2003

Screening procedure for eight quaternary nitrogen muscle relaxants in blood by high-performance liquid chromatography-electrospray ionization mass spectrometry.

A screening procedure was developed for the identification and the quantification of eight quaternary nitrogen muscle relaxants, including d-tubocurarine, alcuronium, pancuronium, vecuronium, atracurium, mivacurium, rocuronium and mebezonium, in blood samples. The procedure involves ion-pair extraction with methylene chloride at pH 5.4, reversed-phase HPLC separation and electrospray ionization mass spectrometry detection. The procedure was validated in terms of linearity (0.929 5 for all the target compounds at 0.1 mg/l). The screening test was found satisfactory and applied in two fatal deaths. In the first case, toxicological investigations on biological fluids collected during the autopsy revealed the presence of vecuronium (1.2 and 0.6 mg/l in blood and urine, respectively) and its desacetylated metabolite, 3-hydroxy-vecuronium (4.4 and 0.7 mg vecuronium equivalent/l in blood and urine, respectively). In the second forensic case, blood analysis showed high levels of mebezonium (6.5 mg/l). The developed procedure was found suitable for forensic investigations.

Adult↗
PubMed2003

Enzyme immunoassay validation for the detection of buprenorphine in urine.

A solid-phase enzyme immunoassay involving microtiter plates was proposed by Microgenics to screen buprenorphine in urine. The intra-assay precision at 10 ng/mL was 7.7% (coefficient of variation). The immunoassay was determined to have no cross-reactivity with codeine, dihydrocodeine, morphine, ethylmorphine, 6-monoacetylmorphine, methadone, pholcodine, propoxyphene, dextromoramide, and dextromethorphan at 1 and 10 mg/L. A low cross-reactivity (3% at 1 ng/mL) was observed at low concentrations of norbuprenorphine. After comparing this new immunological test (Singlestep ELISA) for 76 urine specimens with our validated high-performance liquid chromatography-electrospray mass spectrometry (HPLC-ES-MS) procedure, an optimum cutoff concentration of 2 ng/mL was determined for the kit. At this cutoff, the screening assay was able to determine more than 90% of true results with 43.4% true positives and 48.7% true negatives. Four positive urines (5.3%) were not confirmed by HPLC-ES-MS. In only one case, the negative urine test was confirmed as positive by HPLC-ES-MS (buprenorphine: 62.5 ng/mL). Buprenorphine concentrations determined by HPLC-ES-MS ranged from 1.2 to 1052 ng/mL. Of the four potential adulterants (hypochloride 50 mL/L, sodium nitrite 50 g/L, liquid soap 50 mL/L, and sodium chloride 50 g/L) that might be added to a positive urine specimen, none were able to cause a false-negative response by the immunoassay. The results of this study support the concept that the Singlestep ELISA for buprenorphine determination in urine should be considered as a new, valided screening procedure.

Buprenorphine↗
PubMed2002

Last performance with VIAGRA: post-mortem identification of sildenafil and its metabolites in biological specimens including hair sample.

A 43-year-old man was found dead in a hotel room during a sexual relation with a colleague.He was treated both for cardiovascular disease and for erectile dysfunction with VIAGRA. A pillbox was found in the room with several tablets of verapamil (Isoptine), trimetazidine (Vastarel), yohimbine and bromazepam (Lexomil). A box of VIAGRA 25mg was found in his raincoat and two tablets were missing. His wife declared during the investigation that he was also treated by trinitrine. Autopsy revealed severe coronary artery sclerosis as well as signs of previous myocardial infarctions. Blood, urine, bile, gastric content and hair and representative tissues for histology were collected for toxicological analysis. Sildenafil and yohimbine were screened with liquid chromatography/mass spectrometry (LC/MS) and trinitrine with headspace injection (HS)/GC/MS. Verapamil and trimetazidine were identified and quantified with LC/diode array detection (DAD). Sildenafil was identified in blood, urine, bile and gastric content at 105, 246, 1206 and 754ng/ml, respectively. Hair concentration was 177pg/mg. The desmethyl metabolite was quantified in urine at 143ng/ml. Blood concentrations of verapamil and trimetazidine were measured at 659 and 2133ng/ml, respectively and were above therapeutic ranges. Trinitrine and yohimbine were not identified. These results confirm the absorption of sildenafil, verapamil and trimetazidine before the death and hair analysis indicates the chronic use of sildenafil. To the author's knowledge, this is the first report of a fatal sildenafil-verapamil association, probably by hypotension and cardiac dysrhythmia.

Adult↗
PubMed2002

Doping control for methenolone using hair analysis by gas chromatography-tandem mass spectrometry.

A sensitive, specific and reproducible method for the quantitative determination of methenolone in human hair has been developed. The sample preparation involved a decontamination step of the hair with methylene chloride. The hair sample (about 100 mg) was solubilized in 1 ml 1 M NaOH, 15 min at 95 degrees C, in presence of 1 ng testosterone-d3 used as internal standard. The homogenate was neutralized and extracted using consecutively a solid-phase (Isolute C18 eluted with methanol) and a liquid-liquid (pentane) extraction. The residue was derivatized by adding 50 microl MSTFA-NH4I-2-mercaptoethanol (1000:2:5, v/v/v), then incubated for 20 ml at 60 degrees C. A 1.5-microl aliquot of the derivatized extract was injected into the column (HP5-MS capillary column, 5% phenyl-95% methylsiloxane, 30 m x 0.25 mm I.D., 0.25 microm film thickness) of a Hewlett-Packard (Palo Alto, CA, USA) gas chromatograph (6890 Series). Methenolone was detected by its parent ion at m/z 446 and daughter ions at m/z 208 and 195 through a Finnigan TSQ 700 MS-MS system. The assay was capable of detecting 1 pg/mg of methenolone when approximately 100 mg hair material was processed. Linearity was observed for methenolone concentrations ranging from 2 to 100 pg/mg with a correlation coefficients of 0.965-0.981. Intra-day and between-day precisions at 2, 10 and 25 pg/mg were 10.9-14.1% and 13.7-16.8%, respectively, with an extraction recovery of 97.6%. The analysis of a strand of hair obtained from two bodybuilders, revealed the presence of methenolone at the concentrations of 7.3 and 8.8 pg/mg.

Anabolic Agents↗
PubMed2002

Blood investigation in a fatality involving the veterinary drug T-61.

A case involving an acute fatality resulting from self-administration of about 30 mL of T-61, a euthanasia solution, consisting of a mixture of embutramide, mebezonium, and tetracaine, in a 58-year-old veterinarian is presented. Forensic investigations consisted of an external body examination, during which 5 mL of fluorinated femoral blood was collected. Embutramide and tetracaine were quantitated using gas chromatography coupled to mass spectrometry after extraction with chloroform/isopropanol/n-heptane (50:17:33, v/v) at pH 9.5 and separation on an HP5-MS capillary column. Mebezonium was quantitated using liquid chromatography coupled to mass spectrometry after ion-pair extraction (saturated KI solution) with methylene chloride at pH 5.4 and separation on a 5-mm Nucleosil C18 column. Blood concentrations were 43.0, 6.5, and 0.21 mg/L for embutramide, mebezonium, and tetracaine, respectively. No other drugs, including ethanol, were detected.

Amides↗
PubMed2002

[Crime under the influence of psychoactive drugs: the problem of the duration of detection].

On a regular basis, the media presents the potential risks of the use of psycho-active compounds, including misused pharmaceuticals (flunitrazepam, GHB) or drugs of abuse (cannabis, LSD, ecstasy). Ethanol is also frequently encountered. These drugs can be used for recreational purposes by addicts or can be observed after sexual assaults (drugs spiked in food). Forensic toxicology can be involved in several situations to document impairment, such as: crime under influence, date rape, driving under influence, psychiatric disorders, determination of the cause of death... In some particular situations, it can be very cautious to investigate exposure to psycho-active drugs, due to late sampling of biological specimens. To enhance the window of detection of 3 specific drugs, the authors propose the following: 1. Use of an ultra-sensitive technique, such as GC/MS/MS/NCI for 7-aminoflunitrazepam; 2. Use of a cumulative specimen, such as sweat for GHB and 3. Use of a metabolite with a long half-life, such as ethyl glucuronide for ethanol.

Cause of Death↗
PubMed2002

[Rapid determination of propofol in biological specimens and hair by HS-GC/MS].

This paper proposes an original method for the determination of propofol in biological specimens. For example, hair specimens are cut into small pieces and incubated overnight in Soerensen buffer at 40 degrees C. After headspace preparation of the biological specimens spiked with tetrahydrofurane (internal standard), the analytes are transferred to the gas chromatograph and separated on a HP Wax capillary column. Detection is achieved in SIM mode (propofol: m/z 117, 163 and 178) on a mass spectrometer operating in electronic impact mode. The developed procedure is easy (full-automated), rapid (no extraction- or derivatization-step), sensible and accurate. After validation of the analytical method (linearity, extraction recovery, repeatability, limit of detection), this new procedure was applied to forensic cases.

Anesthetics, Intravenous↗
PubMed2002

Hair analysis of seven bodybuilders for anabolic steroids, ephedrine, and clenbuterol.

Several bodybuilders, all winners of international competitions, were arrested for trafficking of a number of doping agents including anabolic steroids, ephedrine, beta-adrenergics, human chorionic gonadotropin, antidepressants, and diuretics. In accordance with the recent French law against doping, the judge asked to test seven bodybuilders to identify doping practices. Hair and urine specimens were collected for analysis. After decontamination, a 100 mg hair strand was pulverized in a ball mill, hydrolyzed, extracted, and derivatized to be tested by GC/MS for anabolic steroids, beta-adrenergic compounds, ephedrine, and other doping agents. Urine was analyzed for anabolic steroids and metabolites, beta-adrenergic compounds, ephedrine, and human chorionic gonadotropin, in addition to a broad spectrum screening with GC/MS. The following compounds were detected in urine: ephedrine (29 and 36 ng/mL, n = 2), clenbuterol (0.2 to 0.3 ng/mL, n = 3), norandrosterone (4.7 to 100.7 ng/mL, n = 7), norethiocholanolone (0.9 to 161.8 ng/mL, n = 6), stanozolol (1 to 25.8 ng/mL, n = 4), methenolone (2.5 to 29.7 ng/mL, n = 4), testosterone (3 to 59.6 ng/mL, n = 7), epitestosterone (1 to 20.4 ng/mL, n = 7) and ratio testosterone/epitestosterone >6 for four subjects (18.5 to 59.6). The following drugs were detected in hair: ephedrine (0.67 and 10.70 ng/mg, n = 2), salbutamol (15 to 31 pg/mg, n = 3), clenbuterol (15 to 122 pg/mg, n = 6), nandrolone (1 to 7.5 pg/mg, n = 3), stanozolol (2 to 84 pg/mg, n = 4), methenolone (17 and 34 ng/ml, n = 2), testosterone enanthate (0.6 to 18.8 ng/mg, n = 5), and testosterone cypionate (3.3 to 4.8 ng/mg, n = 2). These results document the doping practice and demonstrate repetitive exposure to anabolic compounds and confirm the value of hair analysis as a complement to urinalysis in the control of doping practice.

Adult↗
PubMed2001

Doping control for nandrolone using hair analysis.

A sensitive, specific and reproducible method for the quantitative determination of nandrolone in human hair has been developed. The sample preparation involved a decontamination step of the hair with methylene chloride. The hair sample (about 100 mg) was solubilized in 1 ml NaOH IN, 15 min at 95 degrees C, in presence of 10 ng nandrolone-d(3) used as an internal standard. The homogenate was neutralized and extracted using consecutively a solid phase (Isolute C18) and a liquid--liquid (pentane) extraction. The residue was derivatized by adding 50 microl MSTFA/NH4I/2-mercaptoethanol (1000:2:5; v/v/v), then incubated for 20 min at 60 degrees C. A 4-microl aliquot of the derivatized extract was injected into the column (HP5-MS capillary column, 5% phenyl--95% methylsiloxane, 30 m x 0.25 mm i.d. x 0.25 mm film thickness) of a Hewlett Packard (Palo Alto, CA) gas chromatograph (6890 Series) via a Hewlett Packard (7673) autosampler. The assay was capable of detecting 0.5 pg of nandrolone per mg of hair when approximately 100 mg of hair were processed. Linearity was observed for nandrolone concentrations ranging from 1 to 50 pg/mg with a correlation coefficient of 0.997. Intra-day and between-day precisions at 10 pg/mg were 11.2 and 15.1%, respectively, with an extraction recovery of 81.7%. The analysis of three strands of hair, obtained from three bodybuilders, revealed the presence of nandrolone at the concentration of 1, 3.5 and 7.5 pg/mg.

Doping in Sports↗
PubMed2000

[Drug tests on 198 drivers involved in an accident].

OBJECTIVES: A prospective analytical study was performed in a large population of drivers implicated in traffic accidents to determine the significance of drug levels observed in blood, urine, saliva and sweat and which assays are best to perform in each sample. METHODS: Samples of blood (7.5 ml), urine (10-20 ml), saliva (salivette Sarstedt) and sweat (cosmetic pad spiked with water-isopropanol) were systematically collected in drivers implicated in non-fatal traffic accidents from March to November 1999. The samples were tested for pharmaceuticals (barbiturates, benzodiazepines, anti-depressants, neuroleptics, antiepileptics and antihistamines) and for drugs of abuse by hyphenated chromatographic methods (LC/DAD, GC/MS and LC/MS). RESULTS: A total of 198 drivers (bicycle, motorbike, car, truck) were tested (age range 13-57 years, 82% males). Blood alcohol was positive in 27 cases (13.7%), ranging from 0.11 to 3.19 g/l (mean 1.49 g/l), being > 0.5 g/l in 21 cases. Cannabis was the most frequently observed illicit drug (9.6% of the cases). Its formal pharmacological effect could only be documented by blood testing using GC/MS. Even in the hospital setting, urine collection was difficult. In 16% of the cases, this fluid was missing. Parent compounds were excreted in both saliva and sweat. On-site devices devoted to urine and metabolites were inapplicable. Concentrations in sweat and saliva were very low, particularly for benzodiazepines and cannabis. There was also a risk of external contamination for sweat. CONCLUSION: Saliva might be a good substitution fluid for blood for sample taking on the road side.

Accidents, Traffic↗
PubMed2000

Testing of the anabolic stanozolol in human hair by gas chromatography-negative ion chemical ionization mass spectrometry.

A sensitive, specific and reproducible method for the quantitative determination of stanozolol in human hair has been developed. The sample preparation involved a decontamination step of the hair with methylene chloride and the sonication in methanol of 100 mg of powdered hair for 2 h. After elimination of the solvent, the hair sample was solubilized in 1 ml 1 M NaOH, 15 min at 95 degrees C, in the presence of 10 ng stanozolol-d3 used as internal standard. The homogenate was neutralized and extracted using consecutively a solid-phase (Isolute C18) and a liquid-liquid (pentane) extraction. After evaporation of the final organic phase, the dry extract was derivatized using 40 microl MBHFA-TMSI (1000:20, v/v), incubated for 5 min at 80 degrees C, followed by 10 microl of MBHFBA, incubated for 30 min at 80 degrees C. The derivatized extract was analyzed by a Hewlett-Packard GC-MS system with a 5989 B Engine operating in the negative chemical ionization mode of detection. Linearity of the detector response was observed for stanozolol concentrations ranging from 5 to 200 pg/mg with a correlation coefficient of 0.998. The assay was capable of detecting 2 pg of stanozolol per mg of hair when approximately 100 mg hair material was processed, with a quantification limit set at 5 pg/mg. Intra-day precision was 5.9% at 50 pg/mg and 7.8% at 25 pg/mg with extraction recoveries of 79.8 and 75.1%, respectively. The analysis of a 3-cm long hair strand, obtained from a young bodybuilder (27 year old) assuming to be a regular user of Winstrol (stanozolol, 2 mg), revealed the presence of stanozolol at the concentration of 15 pg/mg.

Adult↗
PubMed2000

Drugs in prehistory: chemical analysis of ancient human hair.

Concern about drug abuse in modern populations has led to the development of specific methods for identification of cocaine, opiates and cannabis in human hair. Drug use in prehistory can provide indirect evidence of interpopulational contact and social stratification. This paper reports drug evaluation in nineteen ancient hair samples from archaeological sites in northern Chile. Each sample was tested for the presence of traces of cocaine, opiates and cannabis, in order to establish a standard methodology for studies of drug use among prehistoric groups. Although results are negative, this absence of evidence could be due to two main causes: (1) the individuals evaluated did not use any drugs, which does not mean that other members of their cultural group did, or (2) the wide range of known drugs studied did not consider some group specific drugs, derived from local or imported plants, thus meaning that a greater drug range must be tested. In any case, our study confirms that drug testing in prehistoric samples is viable. However, in order to determine what kind of substances were used in prehistoric times new patterns that incorporate all drugs which are not part of the western pharmacopeia must be created. Finally, a methodology for the study of drug use among prehistoric groups using ancient hair samples is described.

Cannabinoids↗
PubMed2000

Clozapine dose-concentration relationships in plasma, hair and sweat specimens of schizophrenic patients.

The aim of the present study was to establish an analytical method for the determination of clozapine in sweat and to determine whether the clozapine level in hair and sweat were correlated to the daily dose of clozapine delivered to patients. Twenty-six subjects treated with clozapine at 200-700 mg/day for refractory psychosis were included in the study. Clozapine was determined in plasma by liquid chromatography coupled to a diode array detection system, after extraction with an organic solvent at pH 9.5. Clozapine was extracted from hair and sweat patches specimens by incubation in methanol overnight at 40 degrees C. The residues were analyzed by gas chromatography coupled to mass spectrometry in the electronic impact mode of detection. It was possible to determine clozapine in concentrations ranging from 30 to 1016 ng/ml in plasma (n = 22), from 0.17 to 34.24 ng/mg in hair (n = 23) and from 49 to 5609 ng/patch in sweat (n = 20). Preliminary results suggest a lack of correlation between daily regimen of clozapine and plasma levels of the drug. Therefore, a better dose-concentration relationship was observed in our study between daily dose and hair concentration (r = 0.542, P < 7%) or between daily dose and sweat concentration (r = 0.589, P < 6%), but with wide variations for patients at the same posology. However, the idea of using quantitative drug measurements in hair or sweat to ascertain whether a patient has taken his treatment exactly as prescribed will remain inapplicable.

Antipsychotic Agents↗