RESUMO
A "dilute and shoot" method for measuring norpropoxyphene in human urine using liquid chromatography-tandem mass spectrometry distinguishes two different metabolites of propoxyphene, norpropoxyphene (m/z 326) and a dehydrated rearrangement product (m/z 308). The metabolite formed from the rearrangement and dehydration of norpropoxyphene is excreted in human urine and also may be formed from the chemical degradation of norpropoxyphene. Previously, these two metabolites were indistinguishable by gas chromatography- mass spectrometry methods that use an alkaline extraction that converts norpropoxyphene into its rearrangement product. The degradation of norpropoxyphene presents a challenge for its analytical quantitation, and methods for circumventing these issues are presented.
Assuntos
Analgésicos Opioides/urina , Dextropropoxifeno/urina , Biotransformação , Calibragem , Cromatografia Líquida de Alta Pressão , Dextropropoxifeno/análogos & derivados , Humanos , Indicadores e Reagentes , Padrões de Referência , Soluções , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Propoxyphene was withdrawn from the US market in November 2010. This drug is still tested for in the workplace as part of expanded panel nonregulated testing. METHODS: A convenience sample of urine specimens (n = 7838) were provided by workers from various industries. The percentage of positive specimens with 95% confidence intervals was calculated for each year of the study. Logistic regression was used to assess the impact of the year upon the propoxyphene result. RESULTS: The prevalence of positive propoxyphene tests was much higher before the product's withdrawal from the market. Logistic regression provided evidence of a decreasing linear trend (P < 0.000; ß = -0.71). The odds ratio signifies that for every additional year the urine specimens were 0.49 times less likely to be positive for propoxyphene. CONCLUSIONS: This favors the determination that the change in propoxyphene positive drug test over the years is not by chance. The conclusion supports no longer performing nonregulated workplace propoxyphene urine drug testing for this population.
Assuntos
Dextropropoxifeno/urina , Retirada de Medicamento Baseada em Segurança , Detecção do Abuso de Substâncias/tendências , Local de Trabalho/estatística & dados numéricos , Analgésicos Opioides/urina , Humanos , Meio-Oeste dos Estados Unidos , Estudos RetrospectivosRESUMO
d-Propoxyphene kinetics was studied in 8 healthy male subjects after single oral doses of d-propoxyphene at 65, 130, and 190 mg and after slow intravenous infusion of 65 mg. Total urinary excretion (7 days) indicated complete oral absorption but systemic availability was reduced corresponding to fist-pass elimination of 30% to 70%. There was linearity between oral dose and the corresponding area under the plasma concentration/time curve of d-propoxyphene and the metabolite norpropoxyphene. The kinetic measurements showed 2- to 3-fold interindividual variations: oral clearance, 1.3 to 3.6 1/min; systemic clearance, 0.6 to 1.2 1/min; apparent volume of distribution, 700 to 1,800 1; d-propoxyphene half-life (t1/2), 8 to 24 hr; and norpropoxyphene t1/2, 18 to 29 hr. There were pronounced intraindividual dose-dependent variations in oral clearance in some subjects. The intravenous concentration curves indicated a 3-compartment distribution model.
Assuntos
Dextropropoxifeno/administração & dosagem , Administração Oral , Adulto , Dextropropoxifeno/sangue , Dextropropoxifeno/urina , Avaliação de Medicamentos , Humanos , Injeções Intravenosas , Cinética , MasculinoRESUMO
A baby with neonatal withdrawal from propoxyphene as evidenced by severe diarrhea, flapping tremors, shrill cry, diaphoresis, hypertonicity, and seizures is presented. Propoxyphene and its metabolites were identified in the patient's serum and urine. We express concern about the wide use of propoxyphene and its proposed use in substitution programs for detoxifying and maintaining heroin addicts in view of the possibility of neonatal complications.
Assuntos
Dextropropoxifeno/efeitos adversos , Feto/efeitos dos fármacos , Doenças do Recém-Nascido/induzido quimicamente , Síndrome de Abstinência a Substâncias , Transtornos Relacionados ao Uso de Substâncias , Dextropropoxifeno/sangue , Dextropropoxifeno/urina , Diarreia/induzido quimicamente , Feminino , Humanos , Hipercinese/induzido quimicamente , Recém-Nascido , Masculino , Troca Materno-Fetal , Gravidez , Convulsões/induzido quimicamente , Tremor/induzido quimicamenteRESUMO
Dextropropoxyphene and nordextropropoxyphene were extracted from urine samples with mixed mode solid-phase extraction cartridges. After elution and evaporation to dryness, the eluate was dissolved in mobile phase and each sample was injected in a LC-ESI-MS system. Quantification was carried out in the selected ion monitoring mode. This article shows the possibility to analyse drugs of abuse substances in urine with a single quadrupole mass spectrometer if only a thorough work-up procedure and a sufficient chromatographic separation is accomplished. In order to enhance the fragmentation of the analytes, in-source fragmentation was carried out. One fragment and the pseudomolecular ion per analyte together with chromatographic retention times were sufficient to verify that the sought compound was found in the samples. In- and between day variation was lower than 10% and the recovery was well above 90%. The analytes were quantified in the range 100-10000 ng/ml urine.
Assuntos
Dextropropoxifeno/análogos & derivados , Dextropropoxifeno/urina , Espectrometria de Massas por Ionização por Electrospray/métodos , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The detection of drugs of abuse in urine by four commercial immunoassay systems (TDx, BCL and PFI-20 opiates, and PFI-20 morphine) and one commercial TLC system (Toxi-Lab) was investigated and results compared with those obtained by a dual-column capillary GC system. The TDx system was the most reliable method for preliminary screening of urines for opiates; all the commercial immunoassay systems gave some results which were at variance with those of the GC. The GC method proved to be more reliable than the commercial TLC system in discriminating between the different opiates and is recommended for identification of drugs of abuse in urine specimens in which positive results have been obtained with preliminary screening procedures.
Assuntos
Preparações Farmacêuticas/urina , Transtornos Relacionados ao Uso de Substâncias/urina , Dextropropoxifeno/urina , Estudos de Avaliação como Assunto , Humanos , Imunoensaio/métodos , Entorpecentes/urina , Kit de Reagentes para DiagnósticoRESUMO
Using human cadavers an experimental model was developed to simulate the agonal aspiration of drug- and alcohol-laden vomitus. By needle puncture, an acidified (N/20 HCl) 60-ml slurry of drugs (paracetamol 3.25 g, dextropropoxyphene 325 mg) and ethanol 3% w/v was introduced into the trachea. After 48 h undisturbed at room temperature, blood samples were obtained from ten sites. Ethanol and drug concentrations were highest in the pulmonary vessels in all five cases studied. Pulmonary vein mean ethanol was 58 mg% (range 13-130), paracetamol 969 mg/l (range 284-1934), propoxyphene 70 mg/l (range 11-168). Pulmonary artery mean ethanol was 53 mg% (range 10-98), paracetamol 476 mg/l (range 141-882), propoxyphene 29 mg/l (range 7.6-80). Ethanol and drug concentrations in aortic blood were higher than in the left heart and concentrations in the superior vena cava were higher than in the right heart, suggesting direct diffusion into these vessels rather than diffusion via the pulmonary and cardiac blood. Potential interpretive problems arising from this phenomenon can be avoided by using femoral vein blood for quantitative toxicological analysis.
Assuntos
Acetaminofen/farmacocinética , Dextropropoxifeno/farmacocinética , Etanol/farmacocinética , Pneumonia Aspirativa/patologia , Vômito/metabolismo , Absorção , Acetaminofen/sangue , Acetaminofen/urina , Idoso , Brônquios/metabolismo , Brônquios/patologia , Dextropropoxifeno/sangue , Dextropropoxifeno/urina , Etanol/sangue , Etanol/urina , Feminino , Humanos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pneumonia Aspirativa/metabolismo , Traqueia/metabolismo , Traqueia/patologia , Corpo Vítreo/metabolismoRESUMO
This study evaluated the capability of the Abbott TDx assay to test for propoxyphene in urine and various biological samples, including tissues obtained from three fatal overdoses, by comparison to gas chromatography/mass spectrometry (GC/MS). First, within-run and between-run precision were determined using three control samples (200, 400, and 900 ng/mL) tested over a two-week period. Within-run coefficients of variation (CV) for the three controls were 1.4, 2.2, and 2.5%, respectively; the between-run CVs were 2.5, 3.1, and 4.0%, respectively. The cross-reactivity with norpropoxyphene, the major metabolite of propoxyphene, was concentration dependent and in the range of 29.3 to 92.6%. Propoxyphene and its metabolite were assayed in biological samples the same day using the Abbott TDx and GC/MS. Tissue preparations were analyzed by TDx without specimen pretreatment other than homogenization and dilution with saline. The TDx results were in accordance with the results obtained by GC/MS.
Assuntos
Dextropropoxifeno/análise , Imunoensaio de Fluorescência por Polarização , Cromatografia Gasosa-Espectrometria de Massas , Dextropropoxifeno/urina , Estudos de Avaliação como Assunto , Humanos , Kit de Reagentes para DiagnósticoRESUMO
We have found that in using the Toxi-Lab Spec VC MP3 column we were able to easily identify and quantitate both propoxyphene and the major metabolite, norpropoxyphene, in a single extraction using urine as a matrix. Samples were screened using the Syva EMIT d.a.u. 1.0 assay for propoxyphene on the Olympus 5131, and all presumptive positives were prepared for confirmation by gas chromatography-mass spectrometry on Hewlett-Packard instruments. Urine (1.0 mL) was extracted and treated with a strong base (pH 11.0) in order to rearrange, by base catalysis, norpropoxyphene to norpropoxyphene amide, which chromatographs well on these columns.
Assuntos
Dextropropoxifeno/análogos & derivados , Dextropropoxifeno/urina , Cromatografia Gasosa-Espectrometria de Massas/instrumentação , Cromatografia Gasosa-Espectrometria de Massas/métodos , Dextropropoxifeno/metabolismo , HumanosRESUMO
A gas chromatographic technique with flame ionization detection, which is based on a solid-phase extraction (SPE) procedure using mixed-mode SPE columns, for the simultaneous quantitation of dextropropoxyphene and norpropoxyphene in urine is presented. Urine is treated with sodium hydroxide in order to rearrange, by base catalysis, norpropoxyphene to norpropoxyphene amide, which is then extracted with these columns and chromatographed. The method is specific, linear over the range 0-2000 ng/mL, sensitive, and reproducible. The extracts are cleaner than those obtained with traditional liquid-liquid extraction procedure, which is an important feature in view of further mass spectrometric confirmation of narcotics and other drugs.
Assuntos
Analgésicos Opioides/urina , Cromatografia Gasosa/métodos , Dextropropoxifeno/análogos & derivados , Dextropropoxifeno/urina , Detecção do Abuso de Substâncias/métodos , Ionização de Chama , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores de TempoRESUMO
A new point-of-care colloidal metal immunoassay urine drugs-of-abuse testing device, the BIOSITE TRIAGE Plus Propoxyphene (TPP), was evaluated for the rapid detection of dextropropoxyphene (PPY) and/or its primary metabolite, norpropoxyphene (NP), in urine at a total PPY/NP concentration of 300 ng/mL or greater. This assay has been added to the Triage device that tests for commonly abused drugs. Adding to drug-free urine PPY and NP established the linearity of the TPP assay at concentrations of 40%, 80%, 120%, and 160% of the cut-off concentration. No significant cross-reactivity was found at 1.0 g/L for 32 drugs commonly encountered in emergency department admissions. Significant cross-reactivity was observed only with diphenhydramine and tricyclic antidepressants. TPP results from 160 urine specimens screened for PPY and/or NP were compared to those obtained by testing with DRI enzyme immunoassay, Emit II plus immunoassay, Abuscreen Online immunoassay and gas chromatography-mass spectrometry (GC-MS). There was a 98.8% agreement of positive or negative results between TPP and both the DRI and OnLine assays. The two discordant TPP results were due to concentrations of NP below the TPP minimum cross-reactivity value of 400 ng/mL. These two specimens yielded GC-MS NP concentrations of 262 and 359 ng/mL. These NP concentrations were within +/- 20% of the cross-reactivity cut-off value for NP for TPP, DRI, and Online. There was only an 88% agreement of positive or negative results between TPP and the Emit assay. Twenty urine specimens yielding PPY positive results when tested by TPP were negative by Emit testing. The discordant TPP results were due to poor cross-reactivity of Emit to NP. A 98.8% agreement of positive PPY results was observed between TPP and GC-MS. Discordant urines were found to contain PPY concentrations below the cut-off value of the assay. TPP was found to be an accurate device for the detection of PPY and NP in urine.
Assuntos
Analgésicos Opioides/urina , Dextropropoxifeno/análogos & derivados , Dextropropoxifeno/urina , Detecção do Abuso de Substâncias/instrumentação , Anticorpos/análise , Reações Cruzadas , Reações Falso-Positivas , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Drogas Ilícitas/urina , Imunoensaio , Indicadores e Reagentes , Sistemas On-Line , Sistemas Automatizados de Assistência Junto ao Leito , Reprodutibilidade dos TestesRESUMO
Three cases of multiple false-positive drug tests are described. Postmortem urine specimens were screened using the enzyme-multiplied immunoassay technique. All patients had proteinuria and lactic aciduria. These false-positive reactions were due to the presence of lactate dehydrogenase (LDH), lactic acid, and protein. This finding was confirmed by creating a multiple false-positive sample with a solution of LDH and lactate in 5% bovine serum albumin at pH 6.
Assuntos
Drogas Ilícitas/urina , L-Lactato Desidrogenase/urina , Adulto , Anfetamina/urina , Barbitúricos/urina , Benzodiazepinas/urina , Calibragem , Cocaína/urina , Dextropropoxifeno/urina , Técnica de Imunoensaio Enzimático de Multiplicação , Reações Falso-Positivas , Feminino , Humanos , Lactatos/urina , Ácido Láctico , Masculino , Pessoa de Meia-Idade , Entorpecentes/urina , Mudanças Depois da Morte , Proteinúria , Soroalbumina BovinaRESUMO
In recent years, there has been an increase in the number of reports in the U.S. of the use of drugs, often in conjunction with alcohol, to commit sexual assault. A study was undertaken to assess the prevalence of drug use in sexual assault cases in which substances are suspected of being involved. Law enforcement agencies, emergency rooms, and rape crisis centers across the U.S. were offered the opportunity to submit urine samples collected from victims of alleged sexual assault, where drug use was suspected, for analysis of alcohol and drugs which may be associated with sexual assault. Each sample was tested by immunoassay for amphetamines, barbiturates, benzodiazepines, cocaine metabolite (benzoylecgonine), cannabinoids, methaqualone, opiates, phencyclidine and propoxyphene. The positive screen results were confirmed by gas chromatography-mass spectroscopy (GC-MS). In addition, each sample was tested for flunitrazepam metabolites and gamma-hydroxybutyrate (GHB) by GC-MS and for ethanol by gas chromatography-flame ionization detection (GC-FID). Over a 26-month period, 1179 samples were collected and analyzed from 49 states, Puerto Rico, and the District of Columbia. The states sending the most samples were California (183), Texas (119), Florida (61), Pennsylvania (61), New York (61), Minnesota (50), Illinois (47), Indiana (44), Michigan (40), Maryland (37), Virginia (32), and Massachusetts (31). Four-hundred sixty eight of the samples were found negative for all the substances tested; 451 were positive for ethanol, 218 for cannabinoids, 97 for benzoylecgonine, 97 for benzodiazepines, 51 for amphetamines, 48 for GHB, 25 for opiates, 17 for propoxyphene, and 12 for barbiturates. There were no samples identified as positive for phencyclidine or methaqualone. In addition, 35% of the drug-positive samples contained multiple drugs. This study indicates that, with respect to alleged sexual assault cases, the prevalence of ethanol is very high, followed by cannabinoids, cocaine, benzodiazepines, amphetamines, and GHB. Although only a couple of substances have been implicated with sexual assault, this study has shown that almost 20 different substances have been associated with this crime. This study also raises the concern of illicit and licit drug use in sexual assault cases and suggests the need to test for a range of drugs in these cases. It also highlights the need to test for GHB, which is not generally tested for in a normal toxicology screen.
Assuntos
Drogas Ilícitas/urina , Estupro/estatística & dados numéricos , Benzodiazepinas/urina , Canabinoides/urina , Cocaína/urina , Dextropropoxifeno/urina , Etanol/urina , Feminino , Flunitrazepam/urina , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Imunoensaio , Entorpecentes/urina , Prevalência , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/urinaRESUMO
A series of 137 urine samples were analyzed for drugs of abuse by enzyme immunoassay (EMIT) and by gas chromatography/mass spectrometry (GC/MS). Agreement between these methods was excellent and ranged from 93.4% for benzodiazepines to 98.5% for propoxyphene. EMIT false negative were traced to the presence of elevated endogenous lysozyme or other interfering materials. In the case of moderate amounts of lysozyme the use of a blank would lead to correct results. Disagreement in the identification of nine benzodiazepine samples was found to be due to a low recovery of benzodiazepine metabolites from urine. Recovery could be improved by incubation of the urine sample with the enzyme beta-glucuronidase.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Drogas Ilícitas/urina , Técnicas Imunoenzimáticas , Preparações Farmacêuticas/urina , Benzodiazepinas/urina , Dextropropoxifeno/urina , Estudos de Avaliação como Assunto , Medicina Legal , Muramidase/urina , Proteinúria/urina , ToxicologiaRESUMO
A case of maternal death from pulmonary hypertension secondary to pulmonary granulomatosis is presented. The granulomas are associated with a history of intravenous injection of medications (Ritalin and Talwin) intended for oral use.
Assuntos
Granuloma/etiologia , Metilfenidato , Pentazocina , Complicações na Gravidez , Transtornos Relacionados ao Uso de Substâncias/complicações , Talco/efeitos adversos , Adulto , Dextropropoxifeno/urina , Feminino , Granuloma/patologia , Humanos , Fígado/patologia , Pulmão/patologia , Metilfenidato/urina , Miocárdio/patologia , Pentazocina/urina , GravidezRESUMO
Several problems associated with the gas chromatographic determination of DPX and NDPX are discussed and an improved method for their extraction and quantification is described. The method involves two separate extractions, one for DPX with SKF 525A as the internal standard and one for NPDX with dinor-LAAM as the internal standard. The use of two internal standards improved quantitative reproducibility by almost 50%. It was also found that routine DPX and NDPX assays were better determined on packed columns than on capillary columns because the quality of the samples and of the columns was critical. The use of two IS and the double extraction procedure is recommended for general toxicological analyses.
Assuntos
Dextropropoxifeno/análogos & derivados , Dextropropoxifeno/isolamento & purificação , Cromatografia Gasosa , Dextropropoxifeno/sangue , Dextropropoxifeno/urina , Humanos , Métodos , ToxicologiaRESUMO
Propoxyphene is an opioid analgesic that was surrounded by controversy concerning its safety and efficacy during its lifespan in the US market. Propoxyphene was withdrawn in November of 2010 from the US market and is still being detected one year post-withdrawal in urine specimens from the pain management population. In this study, the prevalence of propoxyphene was determined in a total of 417,914 urine specimens collected from 630 clinics involved in pain management located in 24 states during the period of January 1, 2010, through December 31, 2011. Propoxyphene and norpropoxyphene were measured in urine by a validated liquid chromatography-tandem mass spectrometry procedure with a lower limit of quantitation of 50 ng/mL. The positivity rate for propoxyphene prevalence declined sharply between November and December of 2010 and further declined at a gradual rate, ending in a prevalence of 0.27% (one out of every 370 specimens, n = 25,658) for the month of December 2011. The presented data provide evidence of the dramatic decline in the use of propoxyphene products since their removal from the medical market, and may be beneficial to US urine drug testing programs determining the need for continual monitoring of propoxyphene levels.
Assuntos
Analgésicos Opioides/urina , Dor Crônica/tratamento farmacológico , Dextropropoxifeno/urina , Retirada de Medicamento Baseada em Segurança , Detecção do Abuso de Substâncias/estatística & dados numéricos , Cromatografia Líquida , Dextropropoxifeno/análogos & derivados , Humanos , Manejo de Espécimes , Espectrometria de Massas em Tandem , Estados Unidos , Urinálise/métodosRESUMO
OBJECTIVE: In view of increasing safety concerns, there is a need to assess benefits of use of dextropropoxyphene as opioid substitution treatment, if any. This study aims at urinalysis-based comparative evaluation of pattern of use of dextropropoxyphene and buprenorphine among opioid-dependent subjects. SETTING: Laboratory of a tertiary care drug-dependence treatment center. PARTICIPANTS: Patients on buprenorphine and dextropropoxyphene therapy and their urinalysis records. INTERVENTIONS: Nonexperimental chart review method. MAIN OUTCOME MEASURE(S): "Use," "abuse, "and 'prescribed but not used rates" for buprenorphine and dextropropoxyphene were compared, using chi2-test with level of significance at p < 0.05. RESULTS: Rate of "use" and "abuse" was significantly high for dextropropoxyphene. Rate of 'prescribed but not used" was significantly high for buprenorphine (p < 0.05). CONCLUSIONS: Despite apparent benefits of dextropropoxyphene use in terms of better rates of "use" and 'prescribed but not used" as compared to buprenorphine, one needs to review the situation in light of recent reports of adverse effects with dextropropoxyphene and limited resources available.