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1.
Ther Drug Monit ; 37(4): 451-60, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25549207

RESUMEN

BACKGROUND: Clonazepam, diazepam, and alprazolam are benzodiazepines with sedative, anticonvulsant, and anxiolytic effects, but their prevalence in drug abuse and drug overdoses has long been recognized. When detection times for psychoactive drugs in oral fluid are reported, they are most often based on therapeutic doses administered in clinical studies. Repeated ingestions of high doses, as seen after drug abuse, are however likely to cause positive samples for extended time periods. Findings of drugs of abuse in oral fluid collected from imprisoned persons might lead to negative sanctions, and the knowledge of detection times of these drugs is thus important to ensure correct interpretation. The aim of this study was to investigate the time window of detection for diazepam, clonazepam, and alprazolam in oral fluid from drug addicts admitted to detoxification. METHODS: Twenty-five patients with a history of heavy drug abuse admitted to a detoxification ward were included. Oral fluid was collected daily in the morning and the evening and urine samples every morning for 10 days, using the Intercept device. Whole blood samples were collected if the patient accepted. The cutoff levels in oral fluid were 1.3 ng/mL for diazepam, N-desmethyldiazepam, and 7-aminoclonazepam and 1 ng/mL for clonazepam and alprazolam. In urine, the cutoff levels for quantifications were 30 ng/mL for alprazolam, alpha-OH-alprazolam, and 7-aminoclonazepam, 135 ng/mL for N-desmethyldizepam, and 150 ng/mL for 3-OH-diazepam and for all the compounds, the cutoff for the screening analyses were 200 ng/mL. RESULTS: The maximum detection times for diazepam and N-desmethyldiazepam in oral fluid were 7 and 9 days, respectively. For clonazepam and 7-aminoclonazepam, the maximum detection times in oral fluid were 5 and 6 days, respectively. The maximum detection time for alprazolam in oral fluid was 2.5 days. New ingestions were not suspected in any of the cases, because the corresponding concentrations in urine were decreasing. Results from blood samples revealed that high doses of benzodiazepines had been ingested before admission, and explains the longer detection times in oral fluids than reported previously after intake of therapeutic doses of these drugs. CONCLUSIONS: This study has shown that oral fluid might be a viable alternative medium to urine when the abuse of benzodiazepines is suspected.


Asunto(s)
Alprazolam/análisis , Clonazepam/análisis , Diazepam/análisis , Saliva/química , Detección de Abuso de Sustancias/métodos , Trastornos Relacionados con Sustancias/metabolismo , Trastornos Relacionados con Sustancias/rehabilitación , Adulto , Alprazolam/orina , Cromatografía Líquida de Alta Presión , Clonazepam/sangre , Clonazepam/orina , Diazepam/sangre , Diazepam/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Espectrometría de Masas en Tándem , Factores de Tiempo , Adulto Joven
2.
Chudoku Kenkyu ; 27(1): 33-8, 2014 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-24724359

RESUMEN

Immunoassays are useful methods for the determination of regulated drugs in clinical and forensic laboratories. Although the Instant-View M-1 (IV M-1) immunoassay kit is frequently used to screen drugs in laboratories in Japan, basic information about the IV M-1 such as its specificity and reactivity is not available. In this study, we determined the specificity and cross-reactivity of IV M-1 for the detection of benzodiazepine-related drugs and their metabolites in urine. The IV M-1 could detect triazolobenzodiazepines such as triazolam in urine at concentrations > or = 300 ng/mL. However, thienodiazepines such as etizolam could not be detected because of lack of cross reactivity. A correlation was observed between the structure of the metabolites and the reactivity of the kit; 4-hydroxy metabolites of alprazolam and triazolam were detectable, whereas a-hydroxy metabolites were not. Furthermore, 7-amino metabolites such as nitrazepam could not be detected at any concentration, including high concentrations. The specificity and reactivity of various kits used for detection of drugs in urine are different. Therefore, it is necessary to consider the basic features of the kit used while assessing the results obtained.


Asunto(s)
Benzodiazepinas/orina , Inmunoensayo/métodos , Juego de Reactivos para Diagnóstico , Detección de Abuso de Sustancias/métodos , Alprazolam/orina , Benzodiazepinas/química , Biomarcadores/orina , Reacciones Cruzadas , Diazepam/análogos & derivados , Humanos , Nitrazepam , Sensibilidad y Especificidad , Relación Estructura-Actividad , Triazolam/orina
3.
J Sep Sci ; 35(21): 2970-7, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22997153

RESUMEN

A simple, accurate, and sensitive microextraction by packed sorbent-gas chromatography-mass spectrometry method has been developed for the simultaneous quantification of four antiepileptic drugs; oxcarbazepine, carbamazepine, phenytoin, and alprazolam in human plasma and urine as a tool for drug monitoring. Caffeine was used as internal standards for the electron ionization mode. An original pretreatment procedure on biological samples, based on microextraction in packed syringe using C(18) as packing material gave high extraction yields (69.92-99.38%), satisfactory precision (RSD < 4.7%) and good selectivity. Linearity was found in the 0.1-500 ng/mL range for these drugs with limits of detection (LODs) between 0.0018 and 0.0036 ng/mL. Therefore, the method has been found to be suitable for the therapeutic drug monitoring of patients treated with oxcarbazepine, carbamazepine, phenytoin, and alprazolam. After validation, the method was successfully applied to some plasma samples from patients undergoing therapy with one or more of these drugs. A comparison of the detection limit with similar methods indicates high sensitivity of the present method over the earlier reported methods. The present method is applied for the analysis of these drugs in the real urine and plasma samples of the epileptic patients.


Asunto(s)
Anticonvulsivantes/análisis , Anticonvulsivantes/aislamiento & purificación , Cromatografía de Gases y Espectrometría de Masas/métodos , Microextracción en Fase Sólida/métodos , Alprazolam/sangre , Alprazolam/aislamiento & purificación , Alprazolam/orina , Anticonvulsivantes/sangre , Anticonvulsivantes/orina , Carbamazepina/análogos & derivados , Carbamazepina/sangre , Carbamazepina/aislamiento & purificación , Carbamazepina/orina , Epilepsia/sangre , Epilepsia/tratamiento farmacológico , Epilepsia/orina , Humanos , Oxcarbazepina , Fenitoína/sangre , Fenitoína/aislamiento & purificación , Fenitoína/orina
4.
J Anal Toxicol ; 43(2): 104-111, 2019 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-30517712

RESUMEN

Benzodiazepines are commonly seen in samples submitted for drug testing of patients, people involved in child welfare cases, work-place drug testing, as well as in drug-facilitated assaults. Limited previous experimental studies are available regarding the excretion of benzodiazepines in urine and oral fluid. The aim of this study was to investigate the concentrations of diazepam and alprazolam in oral fluid and urine for up to 2 weeks after ingestion of a single oral dose in healthy volunteers. A total of 11 healthy volunteers ingested 10 mg diazepam at the start of the study and 0.5 mg alprazolam on Day 3 of the study. A total number of 10 oral fluid samples and 17 urine samples were collected from each participant. The samples were analyzed by liquid chromatography with tandem mass spectroscopy and ultra-high performance liquid chromatography tandem mass spectrometry methods. The median detection time was 252 h for the longest detected diazepam metabolite in urine (oxazepam, range 203-322) and 132 h in oral fluid (N-desmethyldiazepam, range 109-136). For alprazolam, the median detection time was 36 h (metabolite α-OH-alprazolam, range 26-61) in urine and 26 h (alprazolam, range 4-37) in oral fluid. These results show that detection times are only 36 h for alprazolam in urine after intake of a single therapeutic oral dose. For diazepam in urine, detection times were 11 days. Detection times were generally shorter in oral fluid compared to urine. The results could be helpful in the interpretation of diazepam or alprazolam findings in drug testing cases involving urine or oral fluid.


Asunto(s)
Alprazolam/orina , Diazepam/orina , Saliva/química , Administración Oral , Adulto , Alprazolam/análisis , Diazepam/análisis , Femenino , Voluntarios Sanos , Humanos , Cinética , Masculino , Factores de Tiempo , Adulto Joven
5.
J Chromatogr A ; 1602: 30-40, 2019 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-31164227

RESUMEN

Herein we describe a methodology to synthesis polyurethane foam molecularly imprinted polymer (PUF-MIP) by using functional monomer for selective extraction of alprazolam. For this purpose, the various percentages of functional monomer are used to synthesis PUF-MIP of alprazolam. To evaluate the selectivity of synthesized PUF-MIP HPLC analysis is applied by introducing caffeine and methadone as an interference. To optimize the proposed technique, effective parameters in the SPE procedure including pH, flow, and salt present is investigated by experimental design. Finally, this method is evaluated in urine sample to monitor alprazolam dosage. In the optimized condition, the synthesized polymer indicates high selectivity value about 71% for alprazolam and 96.8% recovery for MIPUF compared with non-imprinted polyurethane foam (NIPUF). The linear dynamic range (LDR) of 0.03-60 mg L-1, the limit of detection of 8-10 µg L-1, the relative standard deviation (RSD, n = 3) of 2.88-3.65 % and quantification of 25-30 µg L-1 is obtained for HPLC analysis based on PUF-MIP extraction.


Asunto(s)
Alprazolam/aislamiento & purificación , Monitoreo de Drogas/métodos , Poliuretanos/química , Alprazolam/química , Alprazolam/orina , Cafeína/química , Cromatografía Líquida de Alta Presión , Concentración de Iones de Hidrógeno , Metadona/química , Impresión Molecular , Polímeros/química , Sales (Química)/química , Extracción en Fase Sólida
6.
J Forensic Sci ; 61(2): 573-575, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27404634

RESUMEN

Tanax(®) (T-61) is a euthanasia solution commonly used in veterinary medicine in Europe. It consists of three active components: embutramide, mebezonium iodide, and tetracaine hydrochloride. Human consumption of Tanax(®) (T-61) is usually associated with suicide attempts. In our 15-year-long practice, embutramide was detected only three times but within a short period. First, it was found in the urine of a 42-year-old veterinarian, and the other two observations were made in a 16-year-old young man. Urine samples were analyzed using Shimadzu Prominence TOX.I.S.II. HPLC-DAD system with online SPE extraction system. Both of the two patients denied any intention to die. These cases show that this veterinary drug may also be considered as potential drugs of abuse.


Asunto(s)
Amidas/efectos adversos , Amidas/orina , Compuestos de Amonio Cuaternario/efectos adversos , Trastornos Relacionados con Sustancias/orina , Tetracaína/efectos adversos , Adolescente , Adulto , Alprazolam/orina , Combinación de Medicamentos , Humanos , Masculino , Papaverina/análogos & derivados , Papaverina/orina
7.
Psychopharmacology (Berl) ; 181(2): 364-73, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15830221

RESUMEN

RATIONALE: GABA-A receptor ligands, including benzodiapines, may induce disinhibitory effects that increase the probability of risky decision making. To date, few laboratory studies have examined the acute, dose-related effects of benzodiazepines on human risk-taking behavior. Recent data indicate that in the United States alprazolam is the benzodiazepine most frequently misused for recreational purposes. OBJECTIVES: The present study was designed to demonstrate a dose-response relationship between acute alprazolam administration and human risk taking. Furthermore, this investigation sought to examine: (1) the behavioral mechanisms that may be involved in changes in the probability of risky decision making related to alprazolam administration and (2) risk seeking-related personality variables that may predict drug effects on risk taking. METHODS: Using a laboratory measure of risk taking designed to address acute drug effects, 16 adults were administered placebo, 0.5, 1.0, and 2.0 mg alprazolam in a within-subject repeated-measures design. The risk-taking task presented subjects with a choice between two response options operationally defined as risky and nonrisky. Data analyses examined subjective effects, response rates, distribution of choices between the risky and nonrisky option, trial-by-trial response probabilities, and personality correlates related to drug effects at the 2.0-mg dose. RESULTS: Alprazolam administration produced dose-related changes in subjective effects, response rates, and, most importantly, dose-dependently increased selection of the risky response option. The 2.0-mg dose increased the probability of making consecutive risky responses following a gain on the risky response option. Increases at 2.0 mg were related to a combination of personality scales that included high venturesomeness and novelty seeking and low harm avoidance. CONCLUSIONS: Alprazolam administration produced increases in human risk taking under laboratory conditions. In union with previous studies, the observed shift in trial-by-trial response probabilities suggests that sensitivity to consequences (e.g., oversensitivity to recent rewards) may be an important mechanism in the psychopharmacology of risky decision making. Additionally, risk-seeking personality traits may be predictive of acute drug effects on risk-taking behavior.


Asunto(s)
Alprazolam/administración & dosificación , Toma de Decisiones/efectos de los fármacos , Asunción de Riesgos , Administración Oral , Adulto , Alprazolam/farmacocinética , Alprazolam/orina , Análisis de Varianza , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Moduladores del GABA/administración & dosificación , Moduladores del GABA/farmacocinética , Humanos , Masculino , Placebos , Psicometría/métodos , Encuestas y Cuestionarios , Comprimidos
8.
Forensic Sci Int ; 257: 84-92, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26282513

RESUMEN

Benzodiazepines and zolpidem are generally prescribed as sedative, hypnotics, anxiolytics or anticonvulsants. These drugs, however, are frequently misused in drug-facilitated crime. Therefore, a rapid and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for identification and quantification of benzodiazepines, zolpidem and their metabolites in urine using deuterium labeled internal standards (IS). Urine samples (120 µL) mixed with 80 µL of the IS solution were centrifuged. An aliquot (5 µL) of the sample solution was directly injected into the LC-MS/MS system for analysis. The mobile phases consisted of water and acetonitrile containing 2mM ammonium trifluoroacetate and 0.2% acetic acid. The analytical column was a Zorbax SB-C18 (100 mm × 2.1 mm i.d., 3.5 µm, Agilent). The separation and detection of 18 analytes were achieved within 10 min. Calibration curves were linear over the concentration ranges of 0.5-20 ng/mL (zolpidem), 1.0-40 ng/mL (flurazepam and temazepam), 2.5-100 ng/mL (7-aminoclonazepam, 1-hydroxymidazolam, midazolam, flunitrazepam and alprazolam), 5.0-200 ng/mL (zolpidem phenyl-4-carboxylic acid, α-hydroxyalprazolam, oxazepam, nordiazepam, triazolam, diazepam and α-hydroxytriazolam), 10-400 ng/mL (lorazepam and desalkylflurazepam) and 10-100 ng/mL (N-desmethylflunitrazepam) with the coefficients of determination (r(2)) above 0.9971. The dilution integrity of the analytes was examined for supplementation of short linear range. Dilution precision and accuracy were tested using two, four and ten-folds dilutions and they ranged from 3.7 to 14.4% and -12.8 to 12.5%, respectively. The process efficiency for this method was 63.0-104.6%. Intra- and inter-day precisions were less than 11.8% and 9.1%, while intra- and inter-day accuracies were less than -10.0 to 8.2%, respectively. The lower limits of quantification were lower than 10 ng/mL for each analyte. The applicability of the developed method was successfully verified with human urine samples from drug users (n=21). Direct urine sample injection and optimized mobile phases were introduced for simple sample preparation and high-sensitivity with the desired separation.


Asunto(s)
Benzodiazepinas/orina , Cromatografía Liquida/métodos , Hipnóticos y Sedantes/orina , Piridinas/orina , Espectrometría de Masas en Tándem/métodos , Alprazolam/análogos & derivados , Alprazolam/orina , Flurazepam/análogos & derivados , Flurazepam/orina , Toxicología Forense/métodos , Humanos , Límite de Detección , Triazolam/análogos & derivados , Triazolam/orina , Zolpidem
9.
Neuropsychopharmacology ; 40(13): 2969-80, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26038159

RESUMEN

Humans liberally use ethanol for its facilitating effects on social interactions but its effects on central nervous system function remain underexplored. We have recently described that very low doses of ethanol abolish long-term potentiation (LTP)-like plasticity in human cortex, most likely through enhancement of tonic inhibition [Lücke et al, 2014, Neuropsychopharmacology 39:1508-18]. Here, we studied the effects of low-dose ethanol on long-term depression (LTD)-like plasticity. LTD-like plasticity was induced in human motor cortex by paired associative transcranial magnetic stimulation (PASLTD), and measured as decreases of motor evoked potential input-output curve (IO-curve). In addition, sedation was measured by decreases in saccade peak velocity (SPV). Ethanol in two low doses (EtOH<10mM, EtOH<20mM) was compared to single oral doses of alprazolam (APZ, 1mg) a classical benzodiazepine, and zolpidem (ZLP, 10 mg), a non-benzodiazepine hypnotic, in a double-blinded randomized placebo-controlled crossover design in ten healthy human subjects. EtOH<10mM and EtOH<20mM but not APZ or ZLP enhanced the PASLTD-induced LTD-like plasticity, while APZ and ZLP but not EtOH<10mM or EtOH<20mM decreased SPV. Non-sedating low doses of ethanol, easily reached during social drinking, enhance LTD-like plasticity in human cortex. This effect is most likely explained by the activation of extrasynaptic α4-subunit containing gamma-aminobutyric type A receptors by low-dose EtOH, resulting in increased tonic inhibition. Findings may stimulate cellular research on the role of tonic inhibition in regulating excitability and plasticity of cortical neuronal networks.


Asunto(s)
Depresores del Sistema Nervioso Central/administración & dosificación , Etanol/administración & dosificación , Corteza Motora/efectos de los fármacos , Corteza Motora/fisiología , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Administración Oral , Adulto , Alprazolam/administración & dosificación , Alprazolam/sangre , Alprazolam/orina , Depresores del Sistema Nervioso Central/sangre , Depresores del Sistema Nervioso Central/orina , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Electromiografía , Etanol/sangre , Etanol/orina , Potenciales Evocados Motores/efectos de los fármacos , Mano/fisiología , Humanos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/sangre , Hipnóticos y Sedantes/orina , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiología , Piridinas/administración & dosificación , Piridinas/sangre , Piridinas/orina , Estimulación Magnética Transcraneal/métodos , Adulto Joven , Zolpidem
10.
Clin Pharmacol Ther ; 59(5): 514-9, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8646822

RESUMEN

OBJECTIVE: To assess the possible involvement of CYP3A4 in the metabolism of alprazolam in vivo. METHOD: Twelve healthy male volunteers were randomly allocated to one of the two different treatment sequences, placebo-erythromycin or erythromycin-placebo, with an at least 6-week washout period between the two trial phases. Each volunteer received 400 mg erythromycin or matched placebo given orally three times a day for 10 days and an oral dose (0.8 mg) of alprazolam on the posttreatment day 8. Plasma concentration of alprazolam was measured up to 48 hours after the administration, and psychomotor function was assessed at each time of blood samplings with use of the Digit Symbol Substitution Test, visual analog scale, and Udvalg for kliniske undersøgelser side effect rating scale. RESULTS: Erythromycin significantly (p < 0.001) increased the area under the plasma concentration-time curves (200 +/- 43 versus 322 +/- 49 ng . hr/ml from 0 to 48 hours and 229 +/- 52 versus 566 +/- 161 ng . hr/ml from 0 hour to infinity), decreased the apparent oral clearance (1.02 +/- 0.31 versus 0.41 +/- 0.12 ml/min/kg), and prolonged the elimination half-life (16.0 +/- 4.5 versus 40.3 +/- 14.4 hours) of alprazolam. However, any psychomotor function variables did not differ significantly between the erythromycin and placebo trial phases. CONCLUSION: This study suggests that erythromycin, an inhibitor of CYP3A4, inhibits the metabolism of alprazolam, providing an in vivo evidence for the involvement of CYP3A4 in its metabolism. However, the kinetic change of alprazolam by erythromycin does not result in the pharmacodynamic change of this triazolobenzodiazepine, at least after single dosing.


Asunto(s)
Alprazolam/farmacocinética , Ansiolíticos/farmacocinética , Sistema Enzimático del Citocromo P-450/metabolismo , Eritromicina/farmacología , Oxigenasas de Función Mixta/metabolismo , Inhibidores de la Síntesis de la Proteína/farmacología , Administración Oral , Adulto , Alprazolam/administración & dosificación , Alprazolam/sangre , Alprazolam/orina , Ansiolíticos/sangre , Ansiolíticos/orina , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Citocromo P-450 CYP3A , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Interacciones Farmacológicas , Eritromicina/administración & dosificación , Semivida , Humanos , Masculino , Inhibidores de la Síntesis de la Proteína/administración & dosificación , Estadística como Asunto
11.
J Pharm Biomed Anal ; 18(4-5): 667-80, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9919968

RESUMEN

Solid phase micro extraction (SPME) and gas chromatographic analysis was used for the analysis of several benzodiazepines (oxazepam, diazepam, nordiazepam, flunitrazepam and alprazolam) in human urine and plasma. Several factors likely to affect the analyte recovery were screened in a fractional factorial design in order to examine their effect on the extraction recovery. Parameters found significant in the screening were further investigated with the use of response surface methodology. The final conditions for extraction of benzodiazepines were as follows: Octanol was immobilised on a polyacrylate fibre for 4 min. The fibre was placed in the sample and extraction took place at pH 6.0 for 15 min. Urine samples were added to 0.3 g ml(-1) sodium chloride. In plasma, the extraction recovery was less than in urine and releasing the benzodiazepines from plasma proteins followed by protein precipitation was found necessary prior to sampling. The method was validated and found linear over the range of samples. The limits of detection in urine were determined to be in the range 0.01-0.45 micromol l(-1). The corresponding limits of detection in plasma were in the range 0.01-0.48 micromol l(-1). Finally, the method developed was applied to determine some benzodiazepines after administration of a single dose. This method offers sufficient enrichment for bioanalysis after a single dose of high dose benzodiazepines as diazepam, but for low dose benzodiazepines as flunitrazepam, further sensitivity is needed.


Asunto(s)
Ansiolíticos/análisis , Benzodiazepinas/análisis , Cromatografía de Gases/métodos , Alprazolam/análisis , Alprazolam/sangre , Alprazolam/orina , Ansiolíticos/sangre , Ansiolíticos/orina , Benzodiazepinas/sangre , Benzodiazepinas/orina , Diazepam/análisis , Diazepam/sangre , Diazepam/orina , Flunitrazepam/análisis , Flunitrazepam/sangre , Flunitrazepam/orina , Humanos , Concentración de Iones de Hidrógeno , Modelos Químicos , Nordazepam/análisis , Nordazepam/sangre , Nordazepam/orina , Oxazepam/análisis , Oxazepam/sangre , Oxazepam/orina , Proyectos de Investigación
12.
Forensic Sci Int ; 73(1): 49-60, 1995 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-7750882

RESUMEN

Urinary glucuronide metabolites of the benzodiazepines were converted back to the parent molecules after treatment with B-glucuronidase. The benzodiazepines were extracted by a one-step liquid/liquid extraction from urine or by a liquid/solid phase extraction. For the limit of detection (LOD), a standard solution of diazepam and oxazepam was serially diluted and analyzed to the point at which a reproducible analytical result was no longer obtained. Using a temperature program and a splitless mode of injection, excellent quantitation was achieved within an 8-min run time. Based upon specimens obtained from patients under a physician's care, we have determined that urinary concentrations of the benzodiazepines > 200 ng/ml are most likely due to abuse rather than to a prescribed ingestion under strict medical surveillance. Therefore, the calibration standard and cutoff concentration for a positive result was set at 200 ng/ml.


Asunto(s)
Benzodiazepinas/orina , Cromatografía de Gases y Espectrometría de Masas/métodos , Glucuronidasa , Alprazolam/orina , Clordiazepóxido/orina , Clonazepam/orina , Diazepam/orina , Humanos , Lorazepam/orina , Oxazepam/orina , Triazolam/orina
13.
J Anal Toxicol ; 11(6): 247-51, 1987.
Artículo en Inglés | MEDLINE | ID: mdl-3431092

RESUMEN

Alprazolam (Xanax) is a fairly new, yet very popular benzodiazepine tranquilizer. In 1985, it was 6th on a nationwide list of drugs mentioned in emergency room drug poisonings. A procedure was developed that allows alprazolam and its main urinary metabolites, alpha-hydroxyalprazolam and 3-hydroxymethyl-5-methyltriazolyl chlorobenzophenone, to be detected in urine specimens. A dual capillary column, dual nitrogen detector gas chromatographic system was used for reliable identification. Improved chromatographic performance was obtained by acetylating the metabolites. Method characteristics such as linearity, reproducibility, limit of detection, and recovery were determined. The method was tested by assaying urine specimens from hospitalized patients who had been ingesting alprazolam. In most cases, alpha-hydroxyalprazolam was found in the highest concentration and separated best from endogenous urine substances. A single dose concentration-time study was performed, and the time course of alprazolam and metabolite concentrations over 48 hours was determined.


Asunto(s)
Alprazolam/orina , Cromatografía de Gases , Humanos , Hidrólisis , Indicadores y Reactivos , Masculino , Persona de Mediana Edad
14.
J Anal Toxicol ; 16(6): 363-7, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-1293402

RESUMEN

Urine samples containing diazolo- and triazolobenzodiazepines and metabolites were hydrolyzed with beta-glucuronidase and extracted with methylene chloride. The extracts were treated with methyl iodide, methylene chloride, and tetrahexylammonium hydrogen sulfate in basic solution to form the methyl derivatives of the drugs and metabolites. GC/MS analysis resulted in the following test characteristics: day-to-day precision at 360 ng/mL (120 ng/mL for the triazolobenzodiazepine metabolites) was 2.4 to 5.5% CV; calibration curves were linear to 6000 ng/mL (1000 ng/mL for the triazolobenzodiazepine metabolites), and operational limits of quantitation were in the range 13-25 ng/mL.


Asunto(s)
Alprazolam/orina , Benzodiazepinas/orina , Triazolam/orina , Alquilación , Cromatografía de Gases y Espectrometría de Masas , Humanos
15.
J Anal Toxicol ; 16(2): 67-71, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-1501466

RESUMEN

This procedure was developed as an overall benzodiazepine confirmation scheme and includes the detection of the most important urinary analytes encountered by clinical toxicology laboratories in North America: alpha-hydroxyalprazolam, alpha-hydroxytriazolam, 2-hydroxyethylflurazepam, oxazepam, temazepam, and lorazepam. Desmethyldiazepam (nordiazepam) was not targeted because it is metabolized to oxazepam. This procedure takes advantage of beta-glucuronidase hydrolysis for analysis of intact benzodiazepine molecules, oxazepam-2H5 as an internal standard, a newly developed extraction solvent, and a silylating moiety that may be more sensitive than trimethylsilyl (-TMS) derivatives, the tertbutyldimethylsilyl (-TBDMS) derivative. For all compounds the extraction efficiency was greater than 90% and the limit of quantitation (LOQ at a S/N of 10) was less than 10 ng/mL. Coefficients of variation for a 200-ng/mL control were less than 5% and less than or equal to 11% for within-run and between-run trials, respectively. Of 13 human specimens screened by EMIT and most with self-reported histories, alpha-hydroxyalprazolam was found in seven (range 49-1264 ng/mL), oxazepam was found in five (72-3897 ng/mL), and lorazepam (476 ng/mL), 2-hydroxyethylflurazepam (2301 ng/mL), and alpha-hydroxytriazolam (106 ng/mL) in one each.


Asunto(s)
Alprazolam/análogos & derivados , Benzodiazepinas/orina , Triazolam/análogos & derivados , Alprazolam/orina , Cromatografía de Gases y Espectrometría de Masas , Humanos , Triazolam/orina
16.
J Anal Toxicol ; 15(1): 25-9, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-2046338

RESUMEN

Alprazolam is a short-acting triazolobenzodiazepine with anxiolytic and antidepressant properties. It has a half-life of 10-15 hours after multiple oral doses. Approximately 20% of an oral dose is excreted unchanged in the urine. The major urinary metabolites are alpha-OH alprazolam glucuronide and 3-HMB benzophenone glucuronide. The objective of this study was to characterize the reactivity of alprazolam and three metabolites in the Abbott ADx and TDx urinary benzodiazepine assays compared with the EMIT d.a.u. benzodiazepine assay. Alprazolam (at 300 ng/mL) gave an equivalent response as the 300 ng/mL low control (nordiazepam). alpha-OH alprazolam gave an equivalent response to this control between 300-500 ng/mL and 4-OH alprazolam between 500-1000 ng/mL. The 3-HMB benzophenone was not positive even at 10,000 ng/mL. The ADx screening assay was positive in 26 of 31 urine specimens collected from alprazolam-treated patients. All 31 of these specimens were confirmed positive for alpha-OH alprazolam by GC/MS after enzymatic hydrolysis and formation of a TMS derivative. For the TDx, 27 of 31 specimens were positive for benzodiazepines and all 31 were confirmed by GC/MS. All 5 of the negative ADx specimens and 4 of 5 TDx specimens contained 150-400 ng/mL of alpha-OH alprazolam. In conclusion, both the ADx and TDx urine benzodiazepine assays are acceptable screening assays for alprazolam use when the alpha-OH alprazolam concentration is greater than 400 ng/mL.


Asunto(s)
Alprazolam/orina , Autoanálisis/instrumentación , Polarización de Fluorescencia , Cromatografía de Gases y Espectrometría de Masas , Humanos , Técnicas para Inmunoenzimas , Estructura Molecular
17.
J Anal Toxicol ; 11(6): 263-6, 1987.
Artículo en Inglés | MEDLINE | ID: mdl-3323671

RESUMEN

Alprazolam (Xanax) and triazolam (Halcion) are relatively new triazolobenzodiazepines that are anxiolytic and hypnotic. This study assesses the reactivity of these drugs and their major metabolites in the EMIT d.a.u. benzodiazepine metabolite assay. Analytical standards of drugs and metabolites and urine specimens from patients receiving these drugs were analyzed by EMIT. Alprazolam and alpha-OH alprazolam gave an equivalent response to the EMIT low calibrator between 0.2 and 0.3 microgram/mL. Triazolam and alpha-OH triazolam were reactive between 0.3 and 0.5 microgram/mL. The assay was positive in 24 out of 27 random urine specimens from alprazolam-treated patients and in 8 out of 19 urine specimens from triazolam-treated patients. Positive urine results were confirmed by measuring the major urinary metabolites alpha-OH alprazolam and alpha-OH triazolam by HPLC. The study demonstrates that the EMIT assay can detect significant amounts of alprazolam and metabolites in the urine. The assay was negative in 58% of the specimens from individuals receiving triazolam, however.


Asunto(s)
Alprazolam/orina , Benzodiazepinas/orina , Triazolam/orina , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Humanos , Técnicas para Inmunoenzimas , Juego de Reactivos para Diagnóstico
18.
J Anal Toxicol ; 17(7): 427-31, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8309217

RESUMEN

Adinazolam is a triazolobenzodiazepine, currently under clinical investigation, that possesses antidepressant and anxiolytic activity. It has a short half-life (less than 3 h), and less than 2% of an oral dose is excreted unchanged. The major urinary metabolite is N-desmethyladinazolam, and minor metabolites are estazolam and alpha-OH-alprazolam. The objective of this study was to characterize the reactivity of adinazolam, N-desmethyladinazolam, and estazolam in the Emit d.a.u. benzodiazepine assay and the Abbott TDx urine (FPIA) benzodiazepine assay. N-desmethyladinazolam and estazolam gave an equivalent response to the Emit cutoff calibrator (300 ng/mL) at 100-200 ng/mL, and adinazolam gave an equivalent response at 200 ng/mL. By FPIA, N-desmethyladinazolam and adinazolam had equivalent net polarization values as the 300-ng/mL low control at 500-1000 ng/mL, and estazolam gave a positive response at 300 ng/mL. Six volunteers received single oral doses of 10, 30, and 50 mg of adinazolam. Urine specimens (N = 7) were collected from 0 to 36 h post-administration. By Emit, all urine specimens at all doses were positive from 2 to 36 h, and all FPIA analyzed specimens were positive from 2 to 24 h. Confirmation testing was performed by HPLC by analyzing for N-desmethyladinazolam. All urine specimens were confirmed positive for N-desmethyladinazolam (greater than 200 ng/mL) except for the blank specimens (time = 0) and 7 of 18 specimens collected 36 h post-administration. In conclusion, both immunoassay screening assays are acceptable for detecting the presence of adinazolam in human urine for up to 24 h after a single oral dose of 10-50 mg.


Asunto(s)
Ansiolíticos , Benzodiazepinas/orina , Inmunoensayo/métodos , Alprazolam/análogos & derivados , Alprazolam/orina , Cromatografía Líquida de Alta Presión , Disacáridos , Estazolam/orina , Técnica del Anticuerpo Fluorescente , Glucuronatos , Humanos , Técnicas para Inmunoenzimas , Toxicología/métodos
19.
J Anal Toxicol ; 20(4): 217-23, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-8835658

RESUMEN

This study included evaluation of five commercially available immunoassays for the detection of alprazolam and triazolam metabolites in urine following single oral doses of these drugs. The products investigated were the EMIT d.a.u. assay, EMIT II assay, Abbott TDx (FPIA) assay, Bio Site TRIAGE device, and the Boehringer Mannheim/Microgenics CEDIA assay for urinary benzodiazepines. Urine specimens were also analyzed quantitatively by gas chromatography-mass spectrometry. Percent cross-reactivity was assessed by analysis of drug free urine containing drug standards at concentrations ranging from 100 to 10,000 ng/mL. The drug standards analyzed were alpha-OH-alprazolam, alpha-OH-triazolam, and alpha-OH-alprazolam glucuronide. The effect of lowering the screening cut-off value to 100 ng/mL, lowering the confirmation cut-off value to 50 and 25 ng/mL and the use of beta-glucuronidase hydrolysis prior to analysis was also studied. Lowering the screening cut-off value and using enzymatic hydrolysis prior to screening increased the positive detection rate for benzodiazepines with the EMIT d.a.u. assay and fluorescence polarization immunoassay (FPIA). The TRIAGE device gave the lowest percent cross-reactivity in the analysis of the drug standards and gave negative results in all urine specimens analyzed following ingestion of alprazolam and triazolam.


Asunto(s)
Alprazolam/análogos & derivados , Alprazolam/orina , Cromatografía de Gases y Espectrometría de Masas/métodos , Inmunoensayo/métodos , Detección de Abuso de Sustancias/métodos , Triazolam/análogos & derivados , Triazolam/orina , Alprazolam/metabolismo , Reacciones Cruzadas , Técnica de Inmunoensayo de Enzimas Multiplicadas , Inmunoensayo de Polarización Fluorescente/métodos , Valores de Referencia , Triazolam/metabolismo , Urinálisis
20.
J Anal Toxicol ; 19(6): 511-3, 1995 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8926747

RESUMEN

Screening and analysis of the numerous benzodiazepines presents a challenge for the forensic toxicologist. The newer benzodiazepines, which are prescribed in daily dose regimens of 0.5-3 mg, are particularly difficult to screen and analyze. Frequently, history or careful investigation by the medical examiner is the only clue that the laboratory has to follow. We describe four cases involving alprazolam and the modification of an existing serum high-performance liquid chromatographic (HPLC) procedure, which allowed us to analyze whole blood. This HPLC procedure for alprazolam uses a protein precipitation step followed by solid-phase extraction. The method is sensitive to 18 ng/mL and linear from 18 to 200 ng/mL. Reproducibility was determined by extracting and analyzing duplicate samples on five separate occasions. The recovery averaged 84% using postmortem blood spiked with 18 and 150 ng/mL alprazolam.


Asunto(s)
Alprazolam/sangre , Ansiolíticos/sangre , Cromatografía Líquida de Alta Presión/métodos , Adulto , Alprazolam/metabolismo , Alprazolam/orina , Ansiolíticos/metabolismo , Sobredosis de Droga , Femenino , Medicina Legal , Cromatografía de Gases y Espectrometría de Masas , Humanos , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Cambios Post Mortem , Reproducibilidad de los Resultados , Intento de Suicidio
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