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1.
Am Fam Physician ; 99(1): 33-39, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30600984

RESUMO

Urine drug testing is an essential component of monitoring patients who are receiving long-term opioid therapy, and it has been suggested for patients receiving long-term benzodiazepine or stimulant therapy. Family physicians should be familiar with the characteristics and capabilities of screening and confirmatory drug tests. Immunoassays are qualitative tests used for initial screening of urine samples. They can give false-positive and false-negative results, so all results are considered presumptive until confirmatory testing is performed. Immunoassays for opioids may not detect commonly prescribed semisynthetic and synthetic opioids such as methadone and fentanyl; similarly, immunoassays for benzodiazepines may not detect alprazolam or clonazepam. Immunoassays can cross-react with other medications and give false-positive results, which have important implications for a patient's pain treatment plan. False-negative results can cause missed opportunities to detect misuse. Urine samples can be adulterated with other substances to mask positive results on urine drug testing. Family physicians must be familiar with these substances, the methods to detect them, and their effects on urine drug testing.


Assuntos
Analgésicos Opioides/urina , Benzodiazepinas/urina , Fármacos do Sistema Nervoso Central/urina , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Ansiolíticos/urina , Monitoramento de Medicamentos , Reações Falso-Negativas , Reações Falso-Positivas , Medicina de Família e Comunidade , Humanos , Imunoensaio , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/urina
2.
Artigo em Inglês | MEDLINE | ID: mdl-28399467

RESUMO

A novel microextraction technique based on ultrasound-assisted low-density solvent dispersive liquid-liquid microextraction (UA-LDS-DLLME) had been applied for the determination of 4 designer benzodiazepines (phenazepam, diclazepam, flubromazepam and etizolam) in urine samples by gas chromatography- triple quadrupole mass spectrometry (GC-QQQ-MS). Ethyl acetate (168µL) was added into the urine samples after adjusting pH to 11.3. The samples were sonicated in an ultrasonic bath for 5.5min to form a cloudy suspension. After centrifugation at 10000rpm for 3min, the supernatant extractant was withdrawn and injected into the GC-QQQ-MS for analysis. Parameters affecting the extraction efficiency have been investigated and optimized by means of single factor experiment and response surface methodology (Box-Behnken design). Under the optimum extraction conditions, a recovery of 73.8-85.5% were obtained for all analytes. The analytical method was linear for all analytes in the range from 0.003 to 10µg/mL with the correlation coefficient ranging from 0.9978 to 0.9990. The LODs were estimated to be 1-3ng/mL. The accuracy (expressed as mean relative error MRE) was within ±5.8% and the precision (expressed as relative standard error RSD) was less than 5.9%. UA-LDS-DLLME technique has the advantages of shorter extraction time and is suitable for simultaneous pretreatment of samples in batches. The combination of UA-LDS-DLLME with GC-QQQ-MS offers an alternative analytical approach for the sensitive detection of these designer benzodiazepines in urine matrix for clinical and medico-legal purposes.


Assuntos
Benzodiazepinas/urina , Fármacos do Sistema Nervoso Central/urina , Diazepam/análogos & derivados , Cromatografia Gasosa-Espectrometria de Massas/métodos , Microextração em Fase Líquida/métodos , Drogas Desenhadas/farmacocinética , Diazepam/urina , Humanos , Limite de Detecção , Sonicação/métodos , Detecção do Abuso de Substâncias/métodos
3.
J Chromatogr A ; 1248: 24-31, 2012 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-22704883

RESUMO

In this study, a developed technique was reported for extraction and pre-concentration of methamphetamine (MAMP) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) from urine samples using molecularly imprinted-solid phase extraction (MISPE) along with simultaneous derivatization and dispersive liquid-liquid microextraction (DLLME). Molecularly imprinted microspheres as sorbent in solid phase extraction (SPE) procedure were synthesized using precipitation polymerization with MAMP as the template. Aqueous solution of the target analytes was passed through MAMP-MIP cartridge and the adsorbed analytes were then eluted with methanol. The collected eluate was mixed with butylchloroformate which served as the derivatization reagent as well as the extraction solvent. The mixture was immediately injected into deionized water. After centrifugation, 1 µL of the settled organic phase was injected into gas chromatography-flame ionization detection (GC-FID) or gas chromatography-mass spectrometry (GC-MS). Various experimental parameters affecting the performance of both of the steps (MISPE and DLLME) were thoroughly investigated. The calibration graphs were linear in the ranges of 10-1500 ng mL(-1) (MAMP) and 50-1500 ng mL(-1) (MDMA), and the detection limits (LODs) were 2 and 18 ng mL(-1), respectively. The relative standard deviations (%RSDs) obtained for six repeated experiments (100 ng mL(-1) of each drug) were 5.1% and 6.8% for MAMP and MDMA, respectively. The relative recoveries obtained for the analytes in human urine samples, spiked with different levels of each drug, were within the range of 80-88%.


Assuntos
Fármacos do Sistema Nervoso Central/urina , Metanfetamina/urina , Impressão Molecular , N-Metil-3,4-Metilenodioxianfetamina/urina , Extração em Fase Sólida/métodos , Detecção do Abuso de Substâncias/métodos , Calibragem , Fármacos do Sistema Nervoso Central/isolamento & purificação , Cromatografia Gasosa/métodos , Ionização de Chama/métodos , Humanos , Limite de Detecção , Microextração em Fase Líquida/métodos , Metanfetamina/isolamento & purificação , N-Metil-3,4-Metilenodioxianfetamina/isolamento & purificação
4.
Tidsskr Nor Laegeforen ; 131(6): 570-2, 2011 Mar 18.
Artigo em Norueguês | MEDLINE | ID: mdl-21423307

RESUMO

BACKGROUND: In Norway several hundred thousand urine samples are analysed annually to reveal substance abuse. Our laboratory analyses substances with a potential of abuse in about 60,000 urine specimens annually. We wished to find out if our standard panel of analyses can detect most of these substances. MATERIAL AND METHODS: In summer 2009, our department analysed ten substances that were not included in our standard test panel in all urine specimens received on an arbitrarily chosen weekday during five consecutive weeks. In addition, four other laboratories each sent 250 urine specimens to us to be analysed for the same ten substances. RESULTS: 1 854 urine specimens were analysed in total. Substances that were not covered by our standard test panel were detected in 123 samples (6.6 %): i.e. Pregabalin in 83 (4.5 %), methylphenidate in 33 (1.8 %), tramadol in four (0.2 %) and lorazepam in one (0.05 %) sample. The percentage of samples containing substances of abuse not covered by our standard test panel was: 20.8 % in Bergen, 9.8 % in Kristiansand, 8.0 % in Tromsø, 2.8 % in Oslo and 2.3 % in Trondheim. INTERPRETATION: This study indicates that most drugs of abuse are detected by common routine urine analyses. Laboratories that offer analyses of drugs of abuse in urine should have methods available to detect pregabalin and methylphenidate in addition to or included in the standard panel.


Assuntos
Detecção do Abuso de Substâncias , Fármacos do Sistema Nervoso Central/urina , Humanos , Laboratórios Hospitalares/normas , Laboratórios Hospitalares/estatística & dados numéricos , Noruega , Psicotrópicos/urina , Detecção do Abuso de Substâncias/normas , Detecção do Abuso de Substâncias/estatística & dados numéricos
5.
Forensic Sci Int ; 198(1-3): 39-45, 2010 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-20207513

RESUMO

Date-rape drugs (DRDs) are used for the purpose of "drugging" unsuspected victims and raping or robbing them while under the influence of the drug. The wide variety of substances used for criminal purposes, their low concentrations in body fluids and, often, a long time delay between the event and clinical examination make comprehensive screening analysis of biological materials collected from crime victims for the presence of these drugs very difficult. Detection of a drug used to facilitate sexual assault in biological fluids can be very important evidence of a committed crime. The purpose of this study was to develop a simple GC-EI-MS screening procedure for date-rape drugs in urine. Target analytes were isolated by solid-phase extraction. 2-mL urine samples were extracted and then derivatized by using BSTFA+1%TMCS reagent. Detection of all compounds was based on full-scan mass spectra and for each compound one ion was chosen for further quantification. The method allowed the simultaneous screening, detection and quantification of 128 compounds from different groups (number of compounds): opioids (20), amphetamines (11), GHB and related products (3), hallucinogens (9), benzodiazepines (18), antihistamines (9), antidepressants (14), selective serotonin-reuptake inhibitors (4), antipsychotics (7), barbiturates (7), other sedatives (5), muscle relaxants (2) and other drugs (19). The procedure can easily be expanded to encompass more substances. The developed method appeared to be suitable for screening for the target DRDs. The procedure was successfully applied to the analysis of authentic urine samples collected from victims of rapes and other crimes in routine casework.


Assuntos
Fármacos do Sistema Nervoso Central/urina , Cromatografia Gasosa , Espectrometria de Massas por Ionização por Electrospray , Detecção do Abuso de Substâncias/métodos , Vítimas de Crime , Toxicologia Forense/métodos , Humanos , Estupro
7.
Forensic Sci Int ; 174(2-3): 189-96, 2008 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-17555899

RESUMO

The long-term stability of drugs and metabolites of forensic interest in urine, and preventive measures against their decomposition have been investigated, with special attention to filtration sterilization. An aseptic urine collection kit, which was recently developed based on filtration sterilization, was utilized for the aseptic collection and storage of urine samples. For evaluating preservation measures, methamphetamine (MA), amphetamine (AP), nitrazepam (NZ), estazolam (EZ), 7-aminoflunitrazepam (7AF), cocaine (COC), and 6-acetylmorphine (6AM) were spiked into urine at 500 ng/mL each, and were monitored for 6 months at 25, 4, and -20 degrees C, after the addition of NaN(3) and/or filtration sterilization using the aseptic collection kit. In severely contaminated urine with bacteria, there were significant losses of 7AF and NZ, and slight decomposition of MA and AP at 25 degrees C. However, such degradation was successfully suppressed by the use of the kit, though the use of the kit and NaN(3) were preferred for 7AF. The kit was also effective in preventing the hydrolyses of COC and 6AM, while it was suggested that the common preservative NaN(3) can accelerate the hydrolysis of such ester-type drugs and metabolites.


Assuntos
Fármacos do Sistema Nervoso Central/urina , Inibidores da Captação de Dopamina/urina , Estabilidade de Medicamentos , Filtração , Esterilização , Adolescente , Adulto , Anfetamina/urina , Cocaína/urina , Estazolam/urina , Feminino , Flunitrazepam/análogos & derivados , Flunitrazepam/urina , Toxicologia Forense , Humanos , Hidrólise , Indicadores e Reagentes , Masculino , Metanfetamina/urina , Pessoa de Meia-Idade , Derivados da Morfina/urina , Nitrazepam/urina , Azida Sódica , Urina/microbiologia
8.
J Forensic Sci ; 52(5): 1214-8, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17680796

RESUMO

Investigation of a suspected alcohol or drug impaired driving (DUID) case ideally contains several key elements, including a trained officer documenting observations of driving and subject behavior, and collection of a biological specimen for comprehensive toxicology testing. There is currently no common standard of practice among forensic toxicology laboratories in the United States as to which drugs should be tested for, and at what analytical cutoff. Having some uniformity of practice among laboratories would ensure that drugs most frequently associated with driving impairment were consistently evaluated, that appropriate methods were used to screen and confirm the presence of drugs, and that more accurate data were collected on the extent of drug use among drivers. A survey of United States laboratories actively involved in providing analytical support to the Drug Evaluation and Classification Program identified marijuana, benzodiazepines, cocaine, prescription and illicit opiates, muscle relaxants, amphetamines, CNS depressants, and sleep aids used as hypnotics, as being the most frequently encountered drugs in these cases. This manuscript presents recommendations as to what specific members of these drug classes should at a minimum be tested for in the investigation of suspected DUID cases. Additionally we include recommendations for analytical cutoffs for screening and confirmation of drugs in blood and urine. Adopting these guidelines would ensure that the most common drugs would be detected, that laboratories could compare epidemiological findings between jurisdictions, and that aggregate national statistics on alcohol and drug use in drivers involved in fatal injury collisions were representative of the true rates of drug use in the driving population.


Assuntos
Condução de Veículo/legislação & jurisprudência , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Consumo de Bebidas Alcoólicas , Fármacos do Sistema Nervoso Central/sangue , Fármacos do Sistema Nervoso Central/urina , Cromatografia Gasosa/métodos , Toxicologia Forense , Humanos , Imunoensaio , Laboratórios , Entorpecentes/sangue , Entorpecentes/urina , Inquéritos e Questionários , Estados Unidos
9.
Forensic Sci Int ; 171(2-3): 142-50, 2007 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-17158009

RESUMO

A solid-phase microextraction-gas chromatographic-mass spectrometric (SPME-GC-MS) method has been developed and validated for measuring four club drugs in human urine. These drugs include gamma-hydroxybutyrate (GHB), ketamine (KET), methamphetamine (MAMP), and methylenedioxymethamphetamine (MDMA). These drugs are referred to as 'club drugs' because of their prevalence at parties and raves. Deuterium labeled internal standards for each of the four drugs was included in the assay to aid in quantitation. The drugs were spiked into human urine and derivatized using pyridine and hexylchloroformate to make them suitable for GC-MS analysis. The SPME conditions of extraction time/temperature and desorption time/temperature were optimized to yield the highest peak area for each of the four drugs. The final SPME parameters included a 90 degrees C extraction for 20min with a 1min desorption in the GC injector at 225 degrees C using a splitless injection. All SPME work was done using a 100microm PDMS fiber by Supelco. The ratio of pyridine to hexylchloroformate for derivatization was also optimized. The GC separation was carried out on a VF-5ht column by Varian (30m, 0.25mm i.d., 0.10microm film thickness) using a temperature program of 150-270 degrees C at 10 degrees C/min. The instrument used was a ThermoFinnigan Trace GC-Polaris Q interfaced with a LEAP CombiPal autosampler. The data was collected by using extracted ion chromatograms of marker m/z values for each drug from the total ion chromatograms (TIC) (full scan mode). Calibration curves with R(2)>0.99 were generated each day using the peak area ratios (peak area drug/peak area internal standard) versus concentration. The validated method resulted in intra-day and inter-day precision (% R.S.D.) of less than 15% and a % error of less than 15% for four concentrations in the range of 0.05-20microg/mL (MAMP) and 0.10-20microg/mL (GHB, KET, and MDMA). This method has the advantage of an easy sample preparation with acceptable accuracy and precision for the simultaneous quantification of these four drugs of abuse and shows no interference from the urine matrix.


Assuntos
Toxicologia Forense , Cromatografia Gasosa-Espectrometria de Massas , Drogas Ilícitas/urina , Microextração em Fase Sólida , Detecção do Abuso de Substâncias/métodos , Fármacos do Sistema Nervoso Central/química , Fármacos do Sistema Nervoso Central/urina , Formiatos/química , Formiatos/urina , Humanos , Indicadores e Reagentes , Ketamina/química , Ketamina/urina , Metanfetamina/química , Metanfetamina/urina , Estrutura Molecular , N-Metil-3,4-Metilenodioxianfetamina/química , N-Metil-3,4-Metilenodioxianfetamina/urina , Piridinas , Oxibato de Sódio/química , Oxibato de Sódio/urina
10.
Forensic Sci Int ; 157(2-3): 106-16, 2006 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-15899564

RESUMO

Drug screening through urinalysis is a widely accepted tool for rapid detection of potential drug use at a relatively low cost. It is, therefore, a potentially useful method for detecting and monitoring drug use in a variety of contexts such as the criminal justice system, pre-employment screening and a variety of treatment centers. This article explores the efficacy of two commercially available drug-screening assays: Online KIMS assay (Roche) and EMIT II assays. First, we evaluate the sensitivity and specificity of two immunoassays. A total of 738 urine samples were collected among adult arrestee populations from Chicago, New Orleans and Seattle through the Arrestee Drug Abuse Monitoring (ADAM) program. Partial samples were split within one laboratory and analyzed by both enzymes multiplied immunoassay technique (EMIT) II and kinetic interaction of microparticle in solution (KIMS) assays for a 10-drug panel (amphetamine, barbiturates, benzodiazepines, marijuana, cocaine, methadone, methaqualone, opiate, phencyclidine and propoxyphene). Gas chromatography-mass spectrometry (GC-MS) was used as a confirmation method for all positives from either EMIT II or KIMS for all experiments. Second, the paper examines whether using different testing laboratories plays a role in the final results. The same experiments were repeated at two different testing locations: one in California and one in London and England. Third, the paper studies whether drug testing results vary between two laboratories when each of them had used their own routine screening method: the Forensic Science Service (FSS) at Birmingham, United Kingdom with KIMS assay and Medscreen Limited at London, United Kingdom with EMIT II. In summary, both EMIT II and KIMS assays generate fairly consistent results. The concordance rate against each of the 10 drugs tested is relatively high (97.4-100%). The discrepancies, in most cases, occurred at drug concentrations near the cut-off levels. There were more discrepant results between two laboratories compared to when specimens were analyzed at the same laboratory using two different assays.


Assuntos
Técnica de Imunoensaio Enzimático de Multiplicação , Cromatografia Gasosa-Espectrometria de Massas/métodos , Imunoensaio/métodos , Sistemas On-Line , Detecção do Abuso de Substâncias/métodos , Fármacos do Sistema Nervoso Central/urina , Inglaterra , Medicina Legal/métodos , Humanos , Sensibilidade e Especificidade , Estados Unidos
11.
Przegl Lek ; 62(6): 591-4, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16225131

RESUMO

Acute poisonings by medical, narcotic substances and alcohol are actual in Russia in the recent years. Comparison of analytic facilities of modern analytical techniques: chromatographic (HPLC, GC, GC-MS) and immuno-chemical (FPIA) in clinical toxicology for urgent diagnostics, assessment of the severity of acute poisoning and the efficacy of the treatment in patients with acute poisonings by psychotropic drugs, narcotics and alcohol have been done. The object of the study were serum, blood, urine of 611 patients with acute poisonings by amitriptyline, clozapine, carbamazepine, opiates and also alcohol. Threshold concentrations (threshold, critical and lethal) of the toxicants and their active metabolites which corresponded to different degrees of poisoning severity have been determined. The most comfortable and informative screening method for express diagnostics and assessment of severity of acute poisonings by psychotropic drugs and narcotics showed the HPLC with using automatic analyzers. FPIA using the automatic analyzer could be applied for screening studies, if group identification is enough. GC-FID method is advisable in case of poisoning by medical substances and narcotics in view of repeated investigation for assessment of the efficacy of the therapy. GC-MS could be advisable for confirming the results of other methods. GC-TCD possess high sensitivity and specificity and is optimal for express differential diagnostics and quantitative assessment of acute poisoning by ethanol and other alcohols.


Assuntos
Fármacos do Sistema Nervoso Central , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/urina , Doença Aguda , Amitriptilina/sangue , Amitriptilina/intoxicação , Amitriptilina/urina , Carbamazepina/sangue , Carbamazepina/intoxicação , Carbamazepina/urina , Fármacos do Sistema Nervoso Central/sangue , Fármacos do Sistema Nervoso Central/intoxicação , Fármacos do Sistema Nervoso Central/urina , Clozapina/sangue , Clozapina/intoxicação , Clozapina/urina , Etanol/sangue , Etanol/intoxicação , Etanol/urina , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Espectrometria de Massas , Entorpecentes/sangue , Entorpecentes/intoxicação , Entorpecentes/urina , Intoxicação/sangue , Intoxicação/urina , Reprodutibilidade dos Testes , Federação Russa , Índice de Gravidade de Doença , Detecção do Abuso de Substâncias/instrumentação , Toxicologia/normas
12.
Ther Umsch ; 58(4): 226-31, 2001 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-11344954

RESUMO

The extent of drug abuse in mass sport is only poorly documented. Studies about drug abuse investigated only the prohibited substances according to the Olympic movement antidoping code. So for instance about the use of anabolic androgenic steroids (AAS) by school children or young students. But only few investigations point to the drug abuse in mass sport regarding the easily accessible over-the-counter drugs of the class of nonsteroidal anti-inflammatory drugs (NSAID). These drugs permit an athlete to compete at his normal level of performance despite injuries or pain. However, the masking of pain may exacerbate the injury. Precautions should be taken to prevent the unwarranted or unmonitored use of anti-inflammatory agents during treatment of sport injuries. The abuse may be extensive since most people consider over-the-counter drugs, such as aspirin and ibuprofen, harmless. Studies in Switzerland among endurance athletes in mass sport examining the use of medications before an event showed a prevalence between 5 and 10% of NSAID. Even if this seems a small number, further investigations should focus on the use of medications among different age groups and preventive information to abstain from the use of certain medication for competitors in mass sport should be worked out.


Assuntos
Fármacos do Sistema Nervoso Central/efeitos adversos , Dopagem Esportivo/métodos , Medicamentos sem Prescrição/efeitos adversos , Corrida/estatística & dados numéricos , Esportes/tendências , Anti-Inflamatórios não Esteroides/efeitos adversos , Traumatismos em Atletas/prevenção & controle , Cafeína/efeitos adversos , Fármacos do Sistema Nervoso Central/urina , Efedrina/efeitos adversos , Humanos , Salicilatos/efeitos adversos , Suíça
13.
Psychosom Med ; 63(1): 40-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11211063

RESUMO

OBJECTIVE: The effects of exogenous melatonin on sleep, daytime sleepiness, fatigue, and alertness were investigated in 22 patients with delayed sleep phase syndrome whose nocturnal sleep was restricted to the interval from 24:00 to 08:00 hours. This study was a randomized, double-blind, placebo-controlled crossover trial. Subjects received either placebo or melatonin (5 mg) daily for 4 weeks, underwent a 1-week washout period, and then were given the other treatment for an additional 4 weeks. Patients could take the melatonin between 19:00 and 21:00 hours, which allowed them to select the time they felt to be most beneficial for the phase-setting effects of the medication. METHODS: Two consecutive overnight polysomnographic recordings were performed on three occasions: at baseline (before treatment), after 4 weeks of melatonin treatment, and after 4 weeks of placebo treatment. RESULTS: In the 20 patients who completed the study, sleep onset latency was significantly reduced while subjects were taking melatonin as compared with both placebo and baseline. There was no evidence that melatonin altered total sleep time (as compared with baseline total sleep time), but there was a significant decrease in total sleep time while patients were taking placebo. Melatonin did not result in altered scores on subjective measures of sleepiness, fatigue, and alertness, which were administered at different times of the day. After an imposed conventional sleep period (from 24:00 to 08:00), subjects taking melatonin reported being less sleepy and fatigued than they did while taking placebo. CONCLUSIONS: Melatonin ameliorated some symptoms of delayed sleep phase syndrome, as confirmed by both objective and subjective measures. No adverse effects of melatonin were noted during the 4-week treatment period.


Assuntos
Fármacos do Sistema Nervoso Central/administração & dosagem , Melatonina/administração & dosagem , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Sono/efeitos dos fármacos , Adulto , Fármacos do Sistema Nervoso Central/urina , Cronoterapia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Melatonina/urina , Pessoa de Meia-Idade , Polissonografia , Resultado do Tratamento
14.
Yao Xue Xue Bao ; 32(5): 377-83, 1997 May.
Artigo em Chinês | MEDLINE | ID: mdl-11498876

RESUMO

A systematic screening method has been developed for the detection of 29 central nervous system (CNS) drugs in human plasma, urine and gastric juice by high performance capillary electrophoresis (HPCE). The first step is sample preparation. The patient's or normal human plasma (0.5 ml) spiked with CNS drugs was extracted with 2 x 4 ml dichloromethane, while 2 ml of patient's or spiked urine was extracted with 2 x 6 ml chloroform. The combined extract from plasma or urine was evaporated to dryness in a rotation evaporator at 35 degrees C. The residue was dissolved in 100 microliters methanol and subsequently 400 microliters of redistilled water was added. The patient gastric juice (3 ml) was centrifuged at 2,000 r.min-1 for 5 min. The supernatant was filtered through 0.45 micron microporous membrane for injection onto capillary columns. The second step was to perform CZE separation in acidic buffer composed of 30 mmol.L-1(NH4)3PO4(pH 2.50) and 10% acetonitrile (condition A). Most of the benzodiazepines (diazepam, nitrazepam, chlordiazepoxide, flurazepam, extazolam, alprazolam) and methaqualone were baseline separated and detected at 5-13 min, while thiodiphenylamines showed group peaks at 3-5 min and barbiturates migrate with electroosmotic fluid (EOF) together. The third step is to separate the drugs in basic buffer constituted of 70 mmol.L-1 Na2HPO4(pH 8.60) and 30% acetonitrile (condition B). The thiodiphenylamines and some other basic drugs could be well separated, which include thihexyphenidyl, imipramine, amitriptyline, diphenhydramine, chlorpromazine, doxepin, chlorprothixene, promethazine and flurazepam, while the rest of the CNS drugs did not interfere with the separation. The last step was to separate the drugs by micellar electrokinetic chromatography (MEKC) in such a buffer as 70 mmol.L-1 SDS plus 15 mmol.L-1 Na2HPO4 (pH 7.55) and 5% methanol (condition C). Barbiturates (barbital, phenobarbital, methylphenobarbital, amobarbital, thiopental, pentobarbital, secobarbital) and some hydrophobic drugs (glutethimide, alprazolam, clonazepam, carbamazepine, trifluoperazine, oxazepam) could be well separated. These drugs might be identified by both the relative migration time (rtm = tdrug/tEOF) and the ratios of peak heights (rh) monitored at different wavelength, since the ratios are characteristic of the spectrum of a drug. This method has been used in several real clinical samples of intoxication. For example, perphenazine and doxepin were detected in the gastric juice and phenobarbital in blood and gastric juice of an intoxicated patient.


Assuntos
Fármacos do Sistema Nervoso Central/análise , Fármacos do Sistema Nervoso Central/sangue , Fármacos do Sistema Nervoso Central/urina , Doxepina/análise , Eletroforese Capilar/métodos , Suco Gástrico/metabolismo , Humanos , Perfenazina/análise , Fenobarbital/análise , Fenobarbital/sangue
15.
Eur J Drug Metab Pharmacokinet ; 20(2): 135-44, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8582439

RESUMO

The metabolic fate of 9-methyl 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine (MIQ), a compound with promising pharmacological action on the CNS system, was investigated in the rat after an oral dose of 200 mg/kg, the maximal tolerated dose. Urine and feces were collected, exhaustively extracted with organic solvents and the metabolites detected by TLC analysis. The structures of the isolated metabolites were characterized by several mass spectrometry techniques (FD, EI, CI) and, in some cases, confirmed by synthesis. The major metabolic pathways of MIQ in the rat involve: C-oxidation of the methyl group in position 9 to a primary alcohol and to a carboxylic acid, N-oxidation of basic nitrogen and C-oxidation of the quinolizidine nucleus, probably at position 7.


Assuntos
Fármacos do Sistema Nervoso Central/farmacocinética , Quinolizinas/farmacocinética , Animais , Biotransformação , Fármacos do Sistema Nervoso Central/urina , Cromatografia em Camada Fina , Fezes/química , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Oxirredução , Quinolizinas/urina , Ratos , Ratos Sprague-Dawley , Espectrofotometria Ultravioleta
16.
Xenobiotica ; 20(10): 1081-94, 1990 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-2082597

RESUMO

1. The metabolites of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DMPPA; MH-1), in the urine of human volunteers have been investigated. 2. Ten metabolites together with the unchanged drug (MH-1) were isolated by h.p.l.c. and identified by n.m.r. and mass spectrometry as: three metabolites hydroxylated in the pyrrolidine ring of MH-1 (MH-2, MH-3 and MH-4), three metabolites hydroxylated in the dimethylphenyl ring of MH-1 (MH-6, MH-7 and MH-8), N-[(2,6-dimethylphenylcarbamoyl)methyl]-4-hydroxybutyrylamide++ + (MH-5), N-[(2,6-dimethylphenyl-carbamoyl)methyl]succinamic acid (MH-9), the 3-O-sulphate of MH-6 (MH-10) and the 3-O-sulphate of N-(2,6-dimethyl-3-hydroxyphenyl)-2-(5-hydroxy-2-oxo-1-pyrrolidinyl)aceta mide (MH-11). 3. DMPPA was extensively metabolized. The principal metabolic transformations were hydroxylation of the pyrrolidine ring at the C5 carbon followed by oxidative C-N cleavage, and hydroxylation of the phenyl ring followed by sulphate conjugation.


Assuntos
Pirrolidinonas/farmacocinética , Biotransformação , Fármacos do Sistema Nervoso Central/química , Fármacos do Sistema Nervoso Central/farmacocinética , Fármacos do Sistema Nervoso Central/urina , Cromatografia Líquida de Alta Pressão , Humanos , Hidroxilação , Espectroscopia de Ressonância Magnética , Masculino , Estrutura Molecular , Oxirredução , Pirrolidinonas/química , Pirrolidinonas/urina
17.
Ann Clin Biochem ; 27 ( Pt 3): 213-22, 1990 May.
Artigo em Inglês | MEDLINE | ID: mdl-2382955

RESUMO

An external quality assessment survey of testing facilities in UK clinical laboratories for the detection of drugs of abuse was made with nine freeze-dried samples of urine containing representative drugs with their metabolites from the following seven classes; amphetamines and stimulants, barbiturates, cannabinoids, cocaine, minor tranquillisers, opiates and non-opiate narcotics. Reports were received from 120 laboratories. Thirty six per cent of laboratories reported on all seven drug classes and 71% on the five classes excluding cannabinoids and cocaine. A single drug screening technique was used by 32% of laboratories whilst 46% were able to perform tests by both immunological and chromatographic techniques. There was a mean level of false positive reporting of 4.3% and an observed level of false negative reports of 8.4%, the latter underestimating the true frequency. The minor tranquillisers, cocaine and benzoyl ecgonine were the most frequently missed analytes. Several false reports had important potential implications for patient care.


Assuntos
Fármacos do Sistema Nervoso Central/urina , Laboratórios/normas , Antagonistas de Entorpecentes/urina , Garantia da Qualidade dos Cuidados de Saúde , Detecção do Abuso de Substâncias/normas , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Reino Unido
18.
J Chromatogr ; 433: 235-42, 1988 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-3235551

RESUMO

A high-performance liquid chromatographic method for the determination of a novel nootropic agent, N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DM-9384, I), in human serum and urine has been developed. Compound I and the internal standard were extracted with chloroform from alkalinized serum and urine, and the organic layer was evaporated to dryness. The residue was chromatographed on a Nucleosil 7C18 reversed-phase column using 1/15 M potassium dihydrogen-phosphate-acetonitrile (7:3, v/v) as a mobile phase. Quantitation was achieved by monitoring the ultraviolet absorbance at 210 nm. The response was linear (0-2114.0 ng/ml) and the detection limits were 30 ng/ml for serum samples and 50 ng/ml for urine samples. The utility of the assay was demonstrated by determining compound I in serum and urine samples from three healthy male subjects receiving an oral dose of 30 mg of the drug. This method is satisfactorily sensitive and accurate, and is applicable for pharmacokinetic studies of I in humans.


Assuntos
Fármacos do Sistema Nervoso Central/análise , Pirrolidinonas/análise , Fármacos do Sistema Nervoso Central/sangue , Fármacos do Sistema Nervoso Central/urina , Cromatografia Líquida de Alta Pressão , Humanos , Pirrolidinonas/sangue , Pirrolidinonas/urina , Espectrofotometria Ultravioleta
20.
Clin Chem ; 33(2 Pt 1): 319-27, 1987 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2879653

RESUMO

The equipment, methods, logistics, and results of doping-control analyses for the 1984 Los Angeles Olympic Games are discussed in this article. Within 15 days, 1510 different urine specimens underwent 9440 screening analyses by a combination of gas chromatography, gas chromatography-mass spectrometry, "high-performance" liquid chromatography, and radioimmunoassay. These tests covered more than 200 different drugs and metabolites, including psychomotor stimulants, sympathomimetic amines, central nervous system stimulants, narcotic analgesics, and anabolic steroids. The results are summarized by class of drug. Less than 2% of the samples were found to contain a banned drug.


Assuntos
Dopagem Esportivo , Preparações Farmacêuticas/urina , Antagonistas Adrenérgicos beta/urina , Anabolizantes/urina , California , Fármacos do Sistema Nervoso Central/urina , Cromatografia Gasosa , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Entorpecentes/urina , Radioimunoensaio , Simpatomiméticos/urina
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