Publications by authors named "Neil Stowe"

Opioids are widely prescribed pain medications that have the potential for misuse and abuse. As part of a routine procedure, our laboratory frequently encounters questions from clients/Medical Review Officers (MROs) regarding opioid hair concentrations in relation to the amount of opioid taken as part of a prescription. In this manuscript, we have analyzed a large number of real-world examples of opioid hair concentrations following self-reported consumption of an opioid prescription regimen.

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Amphetamines (AMPs) in hair were investigated with thousands of workplace testing head and body hair samples collected and analyzed over 10 years and tabulated by year. All samples were washed by a published extensive method prior to confirmation by liquid chromatography-mass spectrometry-mass spectrometry. Presented are concentrations of parent methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA) and methylenedioxyamphetamine as metabolite and AMP as metabolite and without the presence of parent drug.

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The cannabinoids tetrahydrocannabinol (THC), tetrahydrocannabivarin (THCV), cannabidiol (CBD), cannabinol (CBN) and (-)-11-nor-9-carboxy-∆9-tetrahydrocannabinol (THC-COOH) were determined in 4,773 hair samples. Confirmation of THC-COOH was by GC-MS-MS (gas chromatography--mass spectrometry-mass spectrometry). Confirmation of THC, THCV, CBN and CBD was by LC-MS-MS (liquid chromatoraphy--mass spectrometry-mass spectrometry) on an AB Sciex QTRAP 6500+ LC-MS-MS.

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Hydroxycocaines in hair were investigated with many hundreds of head and body hair samples. All samples were washed by a published extensive aqueous method prior to confirmation by LC-MS/MS. Concentrations, percent of cocaine, and ratios of para- and meta-hydroxycocaines to ortho-hydroxycocaine are presented.

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Opioids, both naturally occurring and semisynthetic, are effective pain management medications, but also possess the potential for abuse. Analyses of over 37,000 head and body hair samples containing codeine, morphine, hydrocodone, hydromorphone, oxycodone or oxymorphone provide a view of use habits of workplace-testing subjects that cannot be obtained from fluid matrices results. Testing was performed using FDA cleared immunoassays using either 2 ng morphine or oxycodone per 10 mg hair as calibrators.

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Analysis of nail clippings may be a useful back-up for hair analysis when hair is unavailable. One aspect of using nails or hair is the ability to analyze whether drug present is from ingestion or from contamination. A common method of three 15-s rinses in methanol failed to remove drug from nails that had been soaked in either 5 or 50 μg/mL cocaine, methamphetamine or morphine for 1 h.

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The presence of the metabolite 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (C-THC) in hair is generally accepted as the definitive proof of delta-9-tetrahydrocannabinol (THC) ingestion. During hair analysis, the removal of any potential C-THC external contamination that could result from marijuana smoke or close personal contact via a wash procedure is critical. Here, we performed a series of experiments to demonstrate that C-THC is the reliable indicator of marijuana ingestion when paired with the correct washing procedure to remove potential external contamination.

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Article Synopsis
  • Botulinum neurotoxin A (BoNT/A) is the most toxic substance and poses a threat as a potential bioweapon due to the lack of approved treatments for exposure.
  • Previous research showed that hydroxamic acid prodrug carbamates can help increase the cellular uptake of BoNT/A, effectively inhibiting its action.
  • The current study builds on this by conducting molecular modeling of BoNT/A and creating a library of new hydroxamic acid derivatives to evaluate their effectiveness in blocking the toxin in both lab and cellular environments.
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Heroin addiction, a chronic relapsing disorder characterized by excessive drug taking and seeking, requires constant psychotherapeutic and pharmacotherapeutic interventions to minimize the potential for further abuse. Vaccine strategies against many drugs of abuse are being developed that generate antibodies that bind drug in the bloodstream, preventing entry into the brain and nullifying psychoactivity. However, this strategy is complicated by heroin's rapid metabolism to 6-acetylmorphine and morphine.

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Simultaneous activation of signaling pathways requires dynamic assembly of higher-order protein complexes at the cytoplasmic domains of membrane-associated receptors in a stimulus-specific manner. Here, using the paradigm of cellular activation through cytokine and innate immune receptors, we demonstrate the proof-of-principle application of small molecule probes for the dissection of receptor-proximal signaling processes, such as activation of the transcription factor NF-κB and the protein kinase p38.

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Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. A vaccine capable of blocking heroin's effects could provide a long-lasting and sustainable adjunct to heroin addiction therapy. Heroin, however, presents a particularly challenging immunotherapeutic target, as it is metabolized to multiple psychoactive molecules.

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Conducting reactions using water as solvent is a highly prized goal for the organic chemist. Based upon recent literature and our continuing interest in the field of aqueous organocatalysis, we tested the scope of an enamine based Diels-Alder reaction using (±)-nornicotine, proline and a proline derivative as aqueous organocatalysts. Unfortunately, none of the examined catalysts under aqueous conditions proved useful, leaving the aqueous Diels-Alder reaction as an elusive goal.

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Botulinum neurotoxin serotype A (BoNT/A) is the most toxic protein known to man and also a bioterrorism agent. As defined by our previous research targeting the etiological agent responsible for BoNT/A intoxication, a protease, we now report on the asymmetric synthesis of four new BoNT/A inhibitors; the most potent of this series is roughly 2-fold more active than the best small molecule inhibitor currently known.

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