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1.
Mil Med ; 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36420960

RESUMO

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder characterized by hyperglycemia of varying degrees. Genetic and lifestyle variations are known to influence the onset and severity of T2DM. Among the genetic variations reported to confer susceptibility to the disease are certain single nucleotide polymorphisms (SNPs). Here, we report the analysis of 18 such SNPs in a military community cohort of 716 subjects, comprising 477 diabetic and 239 control subjects. The population studied included active-duty military personnel, veterans, and their families. The SNPs analyzed in this work occur in nine different genes, comprising six interleukin (IL) genes (IL1A, IL1B, IL4, IL6, IL10, and IL18), fatty acid amide hydrolase (FAAH) gene, and cannabinoid receptors 1 and 2 genes (CNR1, CNR2). The products of these genes are players in different conditions, including inflammation, a process linked with diabetes. MATERIALS AND METHODS: The T2DM and control (no diabetes) DNA samples were acquired from an archived sample repository (Center for Advanced Molecular Detection, 59th Medical Wing, U.S. Air Force, Joint Base San Antonio [JBSA]-Lackland, TX). The blood samples had been previously collected from gender- and race-mixed cohorts under a protocol approved by the 59th Medical Wing Institutional Review Board. Single nucleotide polymorphism (SNP) genotyping was done by real-time Polymerase Chain Reaction (PCR) using TaqMan assay reagents. The statistical analysis software 9.3 (SAS 9.3) was used for statistical analyses to reveal associations between the SNP genotypes and T2DM. RESULTS: Out of the 18 SNPs analyzed, six showed statistically significant association with T2DM in the overall cohort (P < .05). The odds ratio for these associations varied from 1.57 to 3.16. The rs16944 T/T homozygous genotype (IL1B) showed the strongest association with T2DM, with P = .005. In the White cohort, five of these six SNPs and one other, rs806368 (cannabinoid receptor 1), associate with T2DM. However, the gender-specific analysis of the White cohort revealed only two SNP associations with T2DM in the female cohort, rs16944 (IL1B) and rs2295632 (FAAH), both also showing association in the overall mixed cohort. Likewise, four SNPs showed T2DM association in the White male cohort, with rs187238 (IL18) being uniquely significant in this group. CONCLUSIONS: The IL1B SNP rs16944 showed consistent statistically significant association with T2DM and therefore is likely a promising biomarker for T2DM. We note, however, that this association in a generic sense may be with the inflammatory process that accompanies T2DM and not per se with T2DM.

2.
J Med Toxicol ; 16(1): 49-60, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31677050

RESUMO

INTRODUCTION: Non-medical use and abuse of prescription opioids is a growing problem in both the civilian and military communities, with minimal technologies for detecting hydrocodone use. This study explored the proteomic changes that occur in the oral fluid and blood plasma following controlled hydrocodone administration in 20 subjects. METHODS: The global proteomic profile was determined for samples taken at four time points per subject: pre-exposure and 4, 6, or 168 hours post-exposure. The oral fluid samples analyzed herein provided greater differentiation between baseline and response time points than was observed with blood plasma, at least partially due to significant person-to-person relative variability in the plasma proteome. RESULTS: A total of 399 proteins were identified from oral fluid samples, and the abundance of 118 of those proteins was determined to be significantly different upon metabolism of hydrocodone (4 and 6 hour time points) as compared to baseline levels in the oral fluid (pre-dose and 168 hours). CONCLUSIONS: We present an assessment of the oral fluid and plasma proteome following hydrocodone administration, which demonstrates the potential of oral fluid as a noninvasive sample that may reveal features of hydrocodone in opioid use, and with additional study, may be useful for other opioids and in settings of misuse.


Assuntos
Analgésicos Opioides/administração & dosagem , Proteínas Sanguíneas/metabolismo , Hidrocodona/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Proteoma , Proteômica , Saliva/metabolismo , Detecção do Abuso de Substâncias , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/sangue , Valor Preditivo dos Testes , Extração em Fase Sólida , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Fatores de Tempo , Adulto Jovem
3.
Am J Trop Med Hyg ; 97(5): 1477-1481, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28820695

RESUMO

Recent biosurveillance findings at Joint Base San Antonio (JBSA), a large military installation located in south-central Texas, indicate the potential for vector-borne human Chagas disease. A cross-sectional study was conducted to determine the prevalence and seroprevalence of Trypanosoma cruzi infection in highest risk subpopulations on the installation, including students and instructors who work and sleep in triatomine-endemic field settings. Real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and indirect immunofluorescent antibody assay were performed on enrolled subjects (N = 1,033), none of whom tested positive for T. cruzi or anti-T. cruzi antibodies. Current countermeasures used during field training on JBSA appear to be sufficient for preventing autochthonous human Chagas disease.


Assuntos
Doença de Chagas/epidemiologia , Doença de Chagas/transmissão , Militares , Adolescente , Adulto , Animais , Anticorpos Antiprotozoários/sangue , Estudos Transversais , Feminino , Humanos , Insetos Vetores/parasitologia , Masculino , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Texas/epidemiologia , Triatoma/parasitologia , Trypanosoma cruzi/isolamento & purificação , Adulto Jovem
4.
Artigo em Inglês | MEDLINE | ID: mdl-23523877

RESUMO

A selective, sensitive and accurate high-performance liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the quantitation of hydrocodone, hydromorphone and norhydrocodone in human plasma was developed. The internal standard stock solution comprised of hydrocodone-d6, hydromorphone-d6 and norhydrocodone-d3 was added to 0.5 mL plasma samples. Samples were extracted using a copolymeric sorbent (mixed mode) solid phase extraction (SPE) column. Chromatographic separation was carried out using a reversed-phase C18 analytical column with a gradient mobile phase consisting of solvent A=5% acetonitrile with 0.1% formic acid and solvent B=100% acetonitrile. MS analysis was performed using positive electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode. Linearity was established over the range 1-100 ng/mL with correlation coefficients ≥0.998 for all three analytes. The coefficient of variation (CV) of intra-day samples was ≤5.6% at 10 ng/mL. The precision of inter-day (6 days) samples resulted in CVs ≤8.1% at concentrations tested at 2.5, 10 and 25 ng/mL for all three analytes. The lower limit of quantification (LOQ) was 1.0 ng/mL with signal-to-noise (S/N) ratio >10, the limit of detection (LOD) was 0.25 ng/mL with S/N ratio >3 for the drug and its metabolites. Dilution effects, extraction recovery, stability, interference, carryover and ion suppression were also evaluated. This method was successfully applied to human subject plasma samples in support of a hydrocodone pharmacokinetic study.


Assuntos
Cromatografia Líquida/métodos , Hidrocodona/sangue , Hidromorfona/sangue , Espectrometria de Massas em Tandem/métodos , Estabilidade de Medicamentos , Humanos , Hidrocodona/análogos & derivados , Hidrocodona/farmacocinética , Hidromorfona/farmacocinética , Modelos Lineares , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
5.
Artigo em Inglês | MEDLINE | ID: mdl-22939270

RESUMO

Cyanide poisoning occurs in individuals after fire smoke inhalation and after oral ingestion of cyanide. Hydroxocobalamin (HOCbl), a hydroxylated form of vitamin B(12), is often used as an antidote to treat cyanide toxicity. It has a high affinity for cyanide and rapidly removes cyanide from tissue by forming cyanocobalamin (CNCbl). Little information is available on the pharmacokinetics of HOCbl and CNCbl largely because of the lack of analytical methods for analyzing HOCbl and CNCbl. In this study, we developed a new liquid chromatographic mass spectrometric (LC/MS/MS) method for the quantitative analysis of plasma HOCbl and CNCbl in the porcine (Sus scrofa) model. The method uses on-column extraction, reversed phase gradient chromatography, and multiple reaction monitoring (MRM) for quantitation. MRM transitions monitored were 664.7→147.3 and 664.7→359.2 for HOCbl and 678.8→147.3, 678.8→359.1 678.8→457.1 for CNCbl. The limit of detection (LOD) and the lower limit of quantitation (LLOQ) were 1.0 and 1.0 µmole/L, respectively, for plasma HOCbl and 0.1 and 0.5 µmole/L for plasma CNCbl. The within-day and between-day CVs were 4.3 and 6.4% for plasma HOCbl at 500.0 µmole/L and 5.5 and 5.7% for CNCbl at 100.0 µmole/L (n=6). The plasma HOCbl and CNCbl calibrations curves were linear from 100.0 to 2000.0 and 50.0 to 500.0 µmole/L, respectively. Based on 6 separate calibration curves the average linear regression coefficient (R(2)) for both HOCbl and CNCbl was 0.992. The LC/M/MS method was found to be accurate and precise and has been validated by determining the plasma HOCbl and CNCbl concentrations in 11 pigs that were treated with HOCbl for cyanide poisoning.


Assuntos
Cromatografia Líquida/métodos , Hidroxocobalamina/sangue , Hidroxocobalamina/farmacocinética , Cianeto de Potássio/sangue , Cianeto de Potássio/intoxicação , Espectrometria de Massas em Tandem/métodos , Vitamina B 12/sangue , Animais , Hidroxocobalamina/administração & dosagem , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Suínos , Vitamina B 12/farmacocinética
6.
J Anal Toxicol ; 36(7): 507-14, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22782534

RESUMO

Abuse of prescription opioids for non-medical use has been on the rise over the past decade. The most commonly abused opioid is hydrocodone, a frequently prescribed pain medication metabolized by the body to hydromorphone, norhydrocodone and other minor metabolites. This study describes the excretion profile of hydrocodone, hydromorphone and norhydrocodone in urine following a single dose (10 mg) administration of hydrocodone to human subjects (n = 7) and presents a validated liquid chromatography-tandem mass spectrometry method for analysis of the drug and its metabolites. Limit of quantitation was 5 ng/mL for all analytes; limit of detection was 2.5 ng/mL for hydrocodone and norhydrocodone and 5 ng/mL for hydromorphone. Peak concentrations of hydrocodone were found at 3:30-7:00 hours post-dose and were in the range of 612-2,190 ng/mL. Hydromorphone peak concentrations were found at 6:15-26:45 hours post-dose and ranged from 102 to 342 ng/mL. For norhydrocodone, peak concentrations were found at 4:20-13:00 hours post-dose and ranged from 811 to 3,460 ng/mL. Although hydromorphone was found at lower levels than hydrocodone, in six of seven subjects, it persisted for as long as hydrocodone was detected. Norhydrocodone was found at higher levels and lasted for a longer period of time than hydrocodone, thus making the nor-metabolite a valuable tool in evaluating hydrocodone use and/or misuse.


Assuntos
Hidrocodona/urina , Hidromorfona/urina , Detecção do Abuso de Substâncias/métodos , Administração Oral , Analgésicos Opioides/urina , Cromatografia Líquida , Relação Dose-Resposta a Droga , Feminino , Humanos , Limite de Detecção , Masculino , Dor/tratamento farmacológico , Extração em Fase Sólida , Espectrometria de Massas em Tandem
7.
Ann Emerg Med ; 60(4): 415-22, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22424656

RESUMO

STUDY OBJECTIVE: To determine whether hydroxocobalamin will improve survival compared with epinephrine and saline solution controls in a model of cyanide-induced cardiac arrest. METHODS: Forty-five swine (38 to 42 kg) were tracheally intubated, anesthetized, and central venous and arterial continuous cardiovascular monitoring catheters were inserted. Potassium cyanide was infused until cardiac arrest developed, defined as mean arterial pressure less than 30 mm Hg. Animals were treated with standardized mechanical chest compressions and were randomly assigned to receive one of 3 intravenous bolus therapies: hydroxocobalamin, epinephrine, or saline solution (control). All animals were monitored for 60 minutes after cardiac arrest. Additional epinephrine infusions were used in all arms of the study after return of spontaneous circulation for systolic blood pressure less than 90 mm Hg. A sample size of 15 animals per group was determined according to a power of 80%, a survival difference of 0.5, and an α of 0.05. Repeated-measure ANOVA was used to determine statistically significant changes between groups over time. RESULTS: Baseline weight, time to arrest, and cyanide dose at cardiac arrest were similar in the 3 groups. Coronary perfusion pressures with chest compressions were greater than 15 mm Hg in both treatment groups indicating sufficient compression depth. Zero of 15 (95% confidence interval [CI] 0% to 25%) animals in the control group, 11 of 15 (73%; 95% CI 48% to 90%) in the hydroxocobalamin group, and 11 of 15 (73%; 95% CI 48% to 90%) in the epinephrine group survived to the conclusion of the study (P<.001). The proportion of animals with return of spontaneous circulation at 5 minutes was 4 of 15 (27%; 95% CI 10% to 52%), and that of return of spontaneous circulation at 10 minutes was 11 of 15 (73%; 95% CI 48% to 90%) in the 2 treatment groups. Additional epinephrine infusion after return of spontaneous circulation was administered for hypotension in 2 of 11 (18%; 95% CI 4% to 48%) hydroxocobalamin animals and in 11 of 11 (100%; 95% CI 70% to 100%) of the epinephrine animals (P<.001). At 60 minutes, serum lactate was significantly lower in the hydroxocobalamin group compared with the epinephrine group (4.9 [SD 2.2] versus 12.3 [SD 2.2] mmol/L), and the pH was significantly higher (7.34 [SD 0.03] versus 7.15 [SD 0.07]). Serial blood cyanide levels in the hydroxocobalamin group were also lower than that of the epinephrine group from cardiac arrest through the conclusion of the study. CONCLUSION: Intravenous hydroxocobalamin and epinephrine both independently improved survival compared with saline solution control in our swine model of cyanide-induced cardiac arrest. Hydroxocobalamin improved mean arterial pressure and pH, decreased blood lactate and cyanide levels, and decreased the use of rescue epinephrine therapy compared with that in the epinephrine group.


Assuntos
Antídotos/uso terapêutico , Cianetos/intoxicação , Epinefrina/uso terapêutico , Parada Cardíaca/induzido quimicamente , Hidroxocobalamina/uso terapêutico , Animais , Pressão Sanguínea/efeitos dos fármacos , Cianetos/antagonistas & inibidores , Cianetos/sangue , Modelos Animais de Doenças , Epinefrina/administração & dosagem , Feminino , Parada Cardíaca/tratamento farmacológico , Massagem Cardíaca , Concentração de Íons de Hidrogênio , Hidroxocobalamina/administração & dosagem , Injeções Intravenosas , Lactatos/sangue , Masculino , Suínos
8.
Ann Emerg Med ; 55(4): 345-51, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19944487

RESUMO

STUDY OBJECTIVE: Cyanide can cause severe hypotension with acute toxicity. To our knowledge, no study has directly compared hydroxocobalamin and sodium nitrite with sodium thiosulfate in an acute cyanide toxicity model. Our objective is to compare the return to baseline of mean arterial blood pressure between 2 groups of swine with acute cyanide toxicity and treated with hydroxocobalamin with sodium thiosulfate or sodium nitrite with sodium thiosulfate. METHODS: Twenty-four swine were intubated, anesthetized, and instrumented (continuous arterial and cardiac output monitoring) and then intoxicated with a continuous cyanide infusion until severe hypotension. The animals were divided into 2 arms of 12 each and then randomly assigned to intravenous hydroxocobalamin (150 mg/kg)+sodium thiosulfate (413 mg/kg) or sodium nitrite (10 mg/kg)+sodium thiosulfate (413 mg/kg) and monitored for 40 minutes after start of antidotal infusion. Twenty animals were needed for 80% power to detect a significant difference in outcomes (alpha 0.05). Repeated measures of analysis of covariance and post hoc t test were used for determining significance. RESULTS: Baseline mean weights, time to hypotension (31 minutes 3 seconds versus 28 minutes 6 seconds), and cyanide dose at hypotension (5.6 versus 5.9 mg/kg) were similar. One animal in the hydroxocobalamin group and 2 animals in the sodium nitrite group died during antidote infusion and were excluded from analysis. Hydroxocobalamin resulted in a faster return to baseline mean arterial pressure, with improvement beginning at 5 minutes and lasting through the conclusion of the study (P<.05). No statistically significant difference was detected between groups for cardiac output, pulse rate, systemic vascular resistance, or mortality at 40 minutes post intoxication. Mean cyanide blood levels (4.03 versus 4.05 microg/mL) and lactate levels (peak 7.9 versus 8.1 mmol/L) at hypotension were similar. Lactate levels (5.1 versus 4.48 mmol/L), pH (7.40 versus 7.37), and base excess (-0.75 versus 1.27) at 40 minutes were also similar. CONCLUSION: Hydroxocobalamin with sodium thiosulfate led to a faster return to baseline mean arterial pressure compared with sodium nitrite with sodium thiosulfate; however, there was no difference between the antidote combinations in mortality, serum acidosis, or serum lactate.


Assuntos
Antídotos/uso terapêutico , Cianetos/intoxicação , Hidroxocobalamina/uso terapêutico , Nitrito de Sódio/uso terapêutico , Tiossulfatos/uso terapêutico , Acidose/induzido quimicamente , Acidose/tratamento farmacológico , Animais , Antídotos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Hipotensão/induzido quimicamente , Hipotensão/tratamento farmacológico , Lactatos/sangue , Masculino , Monitorização Fisiológica , Sus scrofa , Fatores de Tempo
9.
J Anal Toxicol ; 31(3): 138-43, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17579960

RESUMO

3,4-Methylenedioxymethamphetamine (MDMA), a commonly encountered drug of abuse, has been shown in a variety of studies to cause neurotoxic effects. Because MDMA itself is not neurotoxic, identifying the potential neurotoxic metabolite(s) was of significant importance. Evaluation of urine and plasma concentrations of MDMA and three of its main metabolites, 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxyamphetamine (HMA), and 4-hydroxy-3-methoxymethamphetamine (HMMA), following administration of a neurotoxic dose (20 mg/kg) to male Dark Agouti rats was accomplished. Currently there are no data available describing urine and plasma concentrations of MDMA and these metabolites over a period of 7 days. The rats received a single 20 mg/kg i.p. dose of MDMA. Blood and urine samples were collected prior to administration and at 2, 4, 8, 12, 16, 20, 24, 48, 96, and 168 h following drug administration. Plasma and urine samples were extracted using solid-phase extraction, derivatized with N-methyl-bis(trifluoroacetamide), then analyzed using gas chromatography-mass spectrometry. Urine samples showed peak concentrations of MDMA at 4 h, MDA at 8 h, HMMA at 12 h, and HMA at 16 h post dose. MDMA and its metabolites were detectable (limit of detection 25 ng/mL) in the urine for up to 168 h post dose. Plasma samples showed mean peak concentrations of MDMA and MDA at 2 h post dose and HMMA at 4 h. Although the highest mean concentration of HMA was seen at 24 h post dose, variability between sample results for this time point was significant. No detectable levels of MDMA, MDA, HMA, and HMMA (LOD 10 ng/mL) were found in plasma at 96 and 168 h post dose.


Assuntos
N-Metil-3,4-Metilenodioxianfetamina/sangue , N-Metil-3,4-Metilenodioxianfetamina/urina , Psicotrópicos/sangue , Psicotrópicos/urina , 3,4-Metilenodioxianfetamina/análogos & derivados , 3,4-Metilenodioxianfetamina/sangue , 3,4-Metilenodioxianfetamina/urina , Animais , Biotransformação , Calibragem , Dopamina/análogos & derivados , Dopamina/sangue , Dopamina/urina , Cromatografia Gasosa-Espectrometria de Massas/normas , Masculino , Metanfetamina/análogos & derivados , Metanfetamina/sangue , Metanfetamina/urina , N-Metil-3,4-Metilenodioxianfetamina/farmacocinética , N-Metil-3,4-Metilenodioxianfetamina/toxicidade , Psicotrópicos/farmacocinética , Psicotrópicos/toxicidade , Ratos , Reprodutibilidade dos Testes , Toxicologia/métodos , Toxicologia/normas
10.
J Anal Toxicol ; 28(6): 432-8, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15516292

RESUMO

One of the 14 different drugs known to be metabolized to methamphetamine and/or amphetamine is famprofazone, a component in the multi-ingredient formulation Gewodin. Because of its conversion to methamphetamine and amphetamine, which can result in positive drug-testing results, the excretion pattern of these metabolites is critical for proper interpretation of drug-testing results. Multiple doses of famprofazone were administered to healthy volunteers with no previous history of methamphetamine, amphetamine, or famprofazone use. Following administration, urine samples were collected ad lib for nine days, and pH, specific gravity, and creatinine values were determined. To determine the methamphetamine and amphetamine excretion profile, samples were extracted, derivatized, and analyzed by gas chromatography-mass spectrometry (GC-MS). Peak concentrations of methamphetamine ranged from 5327 to 14,155 ng/mL and from 833 to 3555 ng/mL for amphetamine and were reached between 12:22 and 48:45 h post initial dose. There were 15-19 samples per subject that were positive under HHS testing guidelines, with the earliest at 03:37 h post initial dose and as late as 70:30 h post last dose. Methamphetamine and amphetamine were last detected (LOD > or = 5 ng/mL) up to 159 h and 153 h post last dose for methamphetamine and amphetamine, respectively. GC-MS was also used to determine the enantiomeric composition of methamphetamine and amphetamine. This analysis revealed both enantiomers were present in a predictable pattern.


Assuntos
Metanfetamina/análogos & derivados , Metanfetamina/farmacocinética , Pirazolonas/farmacocinética , Adulto , Anfetamina/urina , Biotransformação , Creatinina/urina , Remoção de Radical Alquila , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Concentração de Íons de Hidrogênio , Metanfetamina/administração & dosagem , Metanfetamina/urina , Pessoa de Meia-Idade , Pirazolonas/administração & dosagem , Padrões de Referência , Estereoisomerismo
11.
J Anal Toxicol ; 28(7): 563-74, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15516315

RESUMO

Interpretation of drug testing results requires detailed scientific information, particularly in those cases where the question of legitimate use versus illicit use arises. Amphetamine remains a widely abused drug throughout the world, although it is also used therapeutically for weight loss, narcolepsy, and attention-deficit disorder with hyperactivity (ADHD). Treatment of ADHD using stimulant drugs is much more common now than it was in even the recent past. Increasingly, older individuals are diagnosed and treated for ADHD, and treatment often continues into adulthood. Amphetamine is commonly used for the treatment of ADHD and is available by prescription as either the d-enantiomer or a mixture of enantiomers. Although used for many years, there are no data available to describe the excretion profile of amphetamine and its enantiomers following repeated use of the drug. As a result, medical review officers (MROs) and forensic toxicologists have no direct evidence to base their decisions on when it comes to evaluation of use of these drugs. The current study was designed to determine the concentration and enantiomer excretion profile following repeated daily administration of mixed enantiomers of amphetamine. Twenty milligrams of Adderall was administered daily to five healthy subjects with all subsequent ad lib urine samples collected for at least five days following administration of the five-dose regimen. Adderall is a 3:1 mixture of d- and l-enantiomers of amphetamine salts and represents the mixed enantiomer proportion of amphetamine available in the United States through pharmaceutical channels. Peak amphetamine concentrations ranged from 5739 to 19,172 ng/mL. Samples containing > or = 500 ng/mL amphetamine (the administrative cutoff for a positive result by gas chromatography-mass spectrometry) were seen up to 60:15 (h:min) following administration of the last dose. Enantiomer analysis showed the d-enantiomer to be in excess of the l-enantiomer for as long as the drug was administered. After administration of the last dose of drug, the proportion of l-enantiomer increased over time. Not all samples that contained > or = 500 ng/mL total amphetamine were positive when tested by immunoassay because of the differing cross-reactivity of the enantiomers. This study provides the first description of the excretion of amphetamine following repeated administration of Adderall. The presence of the l-enantiomer separates this drug from other formulations composed of only the d-enantiomer (i.e., Dexedrine and much illicit amphetamine), thus readily differentiating them from Adderall use. Some illicit and medicinal amphetamine is, however, a mixture of amphetamine enantiomers. Because the enantiomers are metabolized at different rates, their proportion offers the opportunity to describe excretion versus time. Coupling this data with drug concentration makes it possible for forensic toxicologists and MROs to come to an informed decision regarding the involvement of this drug in a positive drug test result.


Assuntos
Anfetamina/urina , Anfetaminas/farmacocinética , Estimulantes do Sistema Nervoso Central/farmacocinética , Dextroanfetamina/urina , Administração Oral , Adulto , Anfetaminas/administração & dosagem , Anfetaminas/urina , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/urina , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Detecção do Abuso de Substâncias , Fatores de Tempo
12.
J Anal Toxicol ; 27(7): 479-84, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14607003

RESUMO

There are a several drugs that lead to the production of methamphetamine and/or amphetamine in the body which are subsequently excreted in the urine. These drugs raise obvious concerns when interpreting positive amphetamine drug testing results. Famprofazone is an analgesic found in a multi-ingredient medication (Gewodin) used for pain relief. Two Gewodin tablets (50 mg of famprofazone) were administered orally to healthy volunteers with no history of amphetamine, methamphetamine, or famprofazone use. Following administration, urine samples were collected ad lib for up to six days, and pH, specific gravity, and creatinine values were determined. In order to determine the quantitative excretion profile of amphetamine and methamphetamine, samples were extracted using liquid-liquid extraction, derivatized with heptafluorobutyric anhydride, and analyzed by gas chromatography-mass spectrometry (GC-MS). The ions monitored were 91, 118, 240 for amphetamine and 254, 210, 118 for methamphetamine. Amphetamine-d(6) and methamphetamine-d(11) were used as internal standards. Peak concentrations for amphetamine ranged from 148 to 2271 ng/mL and for methamphetamine 615 to 7361 ng/mL. Concentrations of both compounds peaked between 3 and 7 h post-dose. Amphetamine and methamphetamine could be detected (limit of detection = 5 ng/mL) at 121 and 143 h post-dose, respectively. Using a cutoff of 500 ng/mL, all subjects had individual urine samples that tested positive. One subject had 14 samples above the cutoff with the last positive being detected over 48 h post-dose. The profile of methamphetamine and amphetamine enantiomers was also determined using liquid-liquid extraction, derivatization with N-trifluoroacetyl-l-prolyl chloride and analysis by GC-MS. Data showed the famprofazone metabolites amphetamine and methamphetamine to be both d- and l-enantiomers. The proportion of l-methamphetamine exceeded that of its d-enantiomer from the first sample collected. Initially, the proportion was approximately 70% l-methamphetamine and this proportion increased over time. Amphetamine results showed l- and d-amphetamine were virtually the same in the early samples with the proportion of l-amphetamine increasing as time progressed. Forensic interpretation of drug testing results is a challenging critical part of forensic drug testing area because of the potential repercussions the results found may have on an individual's life. The finding of each enantiomers by itself differentiates famprofazone use from the most commonly abused form of methamphetamine and all medicinal methamphetamine available in the U.S., which is either d-methamphetamine (prescription medication) or l-methamphetamine (Vicks inhaler). Coupling this information with the concentrations of amphetamine and methamphetamine helps to determine the potential for use of this drug.


Assuntos
Anfetamina , Metanfetamina , Metanfetamina/análogos & derivados , Pirazóis , Pirazolonas , Detecção do Abuso de Substâncias/métodos , Administração Oral , Anfetamina/metabolismo , Anfetamina/urina , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Metanfetamina/administração & dosagem , Metanfetamina/metabolismo , Metanfetamina/urina , Pirazóis/administração & dosagem , Pirazóis/metabolismo , Padrões de Referência , Sensibilidade e Especificidade , Estereoisomerismo , Urinálise
13.
J Anal Toxicol ; 27(7): 485-92, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14607004

RESUMO

Amphetamine remains a widely abused drug throughout the world. It is also used therapeutically for weight loss, narcolepsy, and attention deficit disorder with hyperactivity (ADHD). ADHD has grown dramatically recently both in terms of diagnosis and treatment. Increasingly, older individuals are diagnosed and treated for ADHD, and treatment often continues into adulthood. Of the available treatments for ADHD, Adderall is widely prescribed. Despite its widespread use, there are no published data regarding the expected amphetamine excretion profile following its use. This is problematic because, in this case, medical review officers (MRO) and forensic toxicologists are asked to assess results in terms of use pursuant to valid medical prescription without specific data on which to base a sound decision. To address this situation, a study to determine the concentration and enantiomer composition of amphetamine excretion following administration of Adderall was undertaken. Adderall (20 mg) was administered to five healthy subjects with all subsequent ad lib urine samples (total urine void) collected for seven days. Adderall is a 3:1 mixture of d- and l-enantiomers of amphetamine salts. Peak amphetamine concentrations ranged from 2645 to 5948 ng/mL. Samples containing > or = 500 ng/mL of amphetamine (the administrative cutoff for a positive result by gas chromatography-mass spectrometry) were seen up to 47:30 h post dose. The number of samples that contained amphetamine concentrations of > or = 500 ng/mL ranged among individuals from 7 to 13. As anticipated, analysis showed the d-enantiomer to be in excess of the l-enantiomer, with the proportion of l-enantiomer increasing over time. Because of the mixture of enantiomers, not all samples that contained > or = 500 ng/mL of amphetamine were positive when tested by immunoassay. The drug concentration profiles were quite variable within and between subjects because of dilution and fluctuations in pH of the samples. These results are the first to describe the excretion of amphetamine following administration of Adderall. The presence of the l-enantiomer separates this drug from other preparations of the drug that are composed of only the d-enantiomer (i.e., dexedrine and much illicit amphetamine), thus readily differentiating them from Adderall use. Some illicit and medicinal amphetamine is, however, a mixture of amphetamine enantiomers. Because the enantiomers are metabolized at different rates, their proportion offers the opportunity to describe excretion versus time. Coupling this data with drug concentration makes it possible for forensic toxicologists and MROs to come to an informed decision about the involvement of this drug in a positive drug test result. Using the combination of enantiomer composition and quantitative data will allow MROs and forensic toxicologists to better assess the use of this drug from abuse of amphetamine.


Assuntos
Anfetamina/urina , Anfetaminas/administração & dosagem , Detecção do Abuso de Substâncias/métodos , Administração Oral , Anfetamina/metabolismo , Anfetaminas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Padrões de Referência , Estereoisomerismo , Urinálise
15.
Clin Lab Sci ; 15(2): 111-5, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12776774

RESUMO

Stealth is an adulterant that is advertised as not only preventing a positive drug test in urine, but also to be undetectable by currently available adulteration testing. It has previously been described as a peroxidase and peroxide that is added to urine for the sole purpose of preventing a positive drug test. The product was found to have a significant impact on the ability to detect several drugs of abuse, however, detecting the presence of the adulterant in urine had not yet been reported. A simple procedure to detect the presence of this adulterant in urine was developed. This simple color test procedure using commercially available reagents commonly used in clinical laboratories is based on the use of a chromogen to detect the peroxidase reaction in urine samples. If Stealth is present in the urine, the test sample will show an immediate color change from clear to dark brown. This qualitative test can also be adapted for use with a spectrophotometer or autoanalyzer.


Assuntos
Peroxidase/análise , Detecção do Abuso de Substâncias/métodos , Urinálise/métodos , Enganação , Humanos , Sensibilidade e Especificidade , Espectrofotometria
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