OXFORD, MS, United States

Elsohly Laboratories, Inc.

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OXFORD, MS, United States
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ElSohly M.A.,Elsohly Laboratories, Inc. | ElSohly M.A.,University of Mississippi | Gul W.,Elsohly Laboratories, Inc. | Gul W.,University of Mississippi | And 4 more authors.
Life Sciences | Year: 2014

Cannabimimetics (commonly referred to as synthetic cannabinoids), a group of compounds encompassing a wide range of chemical structures, have been developed by scientists with the hope of achieving selectivity toward one or the other of the cannabinoid receptors CB1 and CB2. The goal was to have compounds that could possess high therapeutic activity without many side effects. However, underground laboratories have used the information generated by the scientific community to develop these compounds for illicit use as marijuana substitutes. This chapter reviews the different classes of these "synthetic cannabinoids" with particular emphasis on the methods used for their identification in the herbal products with which they are mixed and identification of their metabolites in biological specimens.


ElSohly M.A.,Elsohly Laboratories, Inc. | ElSohly M.A.,University of Mississippi | Gul W.,Elsohly Laboratories, Inc. | Gul W.,University of Mississippi | And 4 more authors.
Journal of Analytical Toxicology | Year: 2011

Marijuana is the most widely used drug of abuse all over the world. The major active constituent of the drug is Δ 9-tetrahydrocannabinol (Δ 9-THC). Δ 9-THC exerts its psychological activities by interacting with the cannabinoid receptors (CB 1 and CB 2) in the brain. JWH-018, HU-210, and CP-47497, with CB 1 agonist activity (similar to Δ 9-THC), have been used by the drug culture to spike smokable herbal products to attain psychological effects similar to those obtained by smoking marijuana. The products spiked with these CB 1 agonists are commonly referred to as "Spice" or "K2". The most common compound used in these products is JWH-018 and related compounds (JWH-073 and JWH- 250). Little work has been done on the detection of these synthetic cannabimimetic compounds in biological specimens. This report investigated the metabolism of JWH-018 by human liver microsomes, identification of the metabolites of JWH-018 in urine specimen of an individual who admitted use of the drug, and reports on the quantitation of three of its urinary metabolites, namely the 6-OH-, the N-alkyl OH (terminal hydroxyl)-, and the N-alkyl terminal carboxy metabolites using liquid chromatography-tandem mass spectrometry. The concentrations of these metabolites are determined in several forensic urine specimens.


Hefnawy M.,King Saud University | Al-Omar M.,King Saud University | Julkhuf S.,King Saud University | Attia S.,King Saud University | And 2 more authors.
Analytica Chimica Acta | Year: 2010

Microemulsion electrokinetic capillary chromatography (MEEKC) with sample stacking induced by reverse migrating pseudostationary phase (SRMP) technique in a suppressed electro-osmotic flow (EOF) strategy was investigated for analysing the new ultra-short hypnotic HIE-124 in mice serum. The proposed method utilized fused-silica capillary with a total length of 50cm (effective length 40cm), applied voltages for stacking and separation were 5.0kV for 4.30min and subsequently 25kV, respectively, with a sample injection of 0.5psi for 90s. All the runs were carried out at 25°C and detected at 213nm. The optimum microemulsion background electrolyte (BGE) solution consisted of 0.8% (v/v) ethyl acetate, 6.6% (v/v) butan-2-ol, 1.0% (v/v) acetonitrile, 2.0% (w/v) sodium dodecyl sulfate (SDS), and 89.6mL with 25mM phosphate buffer pH 8. When this preconcentration technique was used, the sample stacking and the separation processes took place successively with changing the voltage with an intermediate polarity switching step. The proposed method was validated carefully with respect to high specificity of the method, good linearity (r=0.9994), fair wide linear concentration range (66-1500ngmL-1), limit of detection and quantitation were 21.6 and 65.5ngmL-1, respectively. The mean relative standard deviation (RSD) of the results of intra- and inter-day precision and accuracy were less than 6.0%, and overall recovery higher than 95% of HIE-124 in mice serum. The developed method could be used for the trace analyses of HIE-124 in serum and was finally used for the pharmacokinetic study investigation of HIE-124 in mice serum. © 2010 Elsevier B.V.


ElSohly M.A.,Elsohly Laboratories, Inc. | ElSohly M.A.,University of Mississippi | Gul W.,Elsohly Laboratories, Inc. | Gul W.,University of Mississippi
Journal of Analytical Toxicology | Year: 2014

There has been a recent rise in the number of cases of athletes being banned from competition because of positive tests for prohibited substances in their biological specimens. Most of these substances are on the World Anti-Doping Agency (WADA) prohibited list, while others are not specifically named on the list. N-Ethyl-α-ethylphenethylamine (ETH), a derivative of phenethylamine (PEA), is one of these unlisted substances and shares chemical and biological effects to the amphetamines, which are listed on the WADA prohibited substances list. It is classified as Category 6B stimulant on the list. This study was directed toward the development of an liquid chromatography tandem mass spectrometry (LC-MS-MS) method for the analysis of ETH in performance-enhancing dietary supplement. A standard was prepared and confirmed by spectroscopic analysis, which was then used to develop the analytical procedure. The procedure was validated and found to have an limit of detection of 2.5 ng/mL, limit of quantification of 5 ng/mL and upper limit of linearity of 500 ng/mL, with within-day variability at the 10-ng/mL level range of 3.88-7.89% (n 5 6) and 1.39-3.36% (n 5 6) for the 100- ng/mL level. The day-to-day variability was 9.8% for the low control and 3.1% for the high control. The method was used to analyze a variety of dietary supplements for ETH as well as PEA and its N, Ndiethyl derivative (NDP). © The Author [2013]. Published by Oxford University Press. All rights reserved.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 205.51K | Year: 2013

DESCRIPTION (provided by applicant): The natural product artemisinin is a sesquiterpene endoperoxide with known anti-malarial activity against both chloroquine-sensitive and chloroquine-resistant strains of the parasite Plasmodium falciparum. In addition to its anti-malarial activity, artemisinin was reported to have cytotoxic activity against several different tumor cell lines. Recently, artemisinin work conducted by our group has been extended to the preparation of a series of dihydroartemisinin dimers (DHA dimers) and the testing of these dimers against protozoal infections, as well as collaborative work with the National Cancer Institute (NCI) and the anti-tumor screening program. The analog DHA dimer oxime and its hemisuccinate ester (HS) have shown very promising results in the NCI screening program and strong activity against malaria in our initial in vitro and in vivo studies. However, the oral antimalarial dose needed was approximately 10-fold higher than the intraperitoneal dose. Several factors could be responsible for the observed limited oral absorption. These could include degradation of the drug/prodrug in the gastrointestinal tract, poor solubility in the gastrointestinal fluids, limited permeability across the gastro-intestinal walls or first-pass metabolism. Thus, the overall objective of this proposal is to elucidate the factor(s) behind the limited oral absorption and to develop formulation(s) that has high oral bioavailability, through strategies to overcome the challenges faced in oral absorption. This will be accomplished through a set of specific aims which include: 1: Synthesis of DHA dimer oxime and DHA dimer oxime hemisuccinate: These are the two compounds characterized as the lead dimers for oral bioavailability studies. 2: Evaluationof the biopharmaceutical characteristics of these DHA dimers: These studies will include solubility, logP, pH stability profile, metabolic stability in te presence of gastrointestinal and hepatic enzymes and in vitro permeability of the compounds. The data obtained will help identify the constraints in oral bioavailability of these compounds. 3: Development of formulation approaches: Based on the findings in Aim 2 various strategies to overcome the challenges including solubilization and stabilization approaches, inclusion of permeation enhancers and nanoparticle dosage forms will be investigated through in vitro permeability experiments. 4: Delineation of oral bioavailability in rats: Finally, promising formulations will be tested in vivo. The oral PK data will be compared to the intraperitoneal PK data. Blood samples will be analyzed using LC/MS/MS. It is anticipated that at least one formulation containing one of the dimers will be identified with high oral bioavailability and willbe progressed to developmental studies during phase II. This STTR application represents a collaborative effort between ElSohly Laboratories, Inc. (ELI), and the Department of Pharmaceutics at the University of Mississippi (UM). PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: This proposal is directed towards improving the oral bioavailability of DHA dimers with potential therapeutic applications in malaria. This novel class of compounds also shows a lot of promise in other infectious diseases and in several forms ofcancer. Development of an orally bioavailable formulation will significantly improve its therapeutic utility and will have a tremendous impact on public health.


PubMed | Elsohly Laboratories, Inc. and University of Mississippi
Type: Journal Article | Journal: Journal of analytical toxicology | Year: 2016

Continuing our previous studies analyzing drugs of abuse in municipal wastewater, a method was developed for the analysis of miscellaneous drugs of abuse in wastewater samples using liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). Eight drugs and metabolites were analyzed including 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrolidine (EDDP), fentanyl, norfentanyl, meperidine, normeperidine, methadone, phencyclidine and tramadol. These drugs were chosen because of their widespread abuse. Wastewater samples were collected at both the Oxford Waste Water Treatment Plant in Oxford, Mississippi (MS) and the University Wastewater Treatment Plant in University, MS. These wastewater samples were collected on weekends in which the University of Mississippi football team (colloquially the Ole Miss Rebels football team) held home games (Vaught-Hemingway Stadium, University, MS 38677). The collected samples were analyzed using a validated method and found to contain tramadol in 25 samples at quantifiable levels. EDDP, meperidine, normeperidine and methadone were also detected but were under the limit of quantitation.


PubMed | Elsohly Laboratories, Inc. and University of Mississippi
Type: Journal Article | Journal: Journal of analytical toxicology | Year: 2016

A method was developed for the analysis of amphetamines and cocaine (Coc) in wastewater samples using liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). Seven stimulant-type drugs and metabolites were analyzed. These drugs included amphetamine (Amp), methamphetamine (Meth), methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA), Coc and benzoylecgonine (BE, the major metabolite of Coc). These drugs were chosen because of their widespread use. Wastewater samples were collected at both the Oxford Waste Water Treatment Plant in Oxford, Mississippi (MS) and the University Wastewater Treatment Plant in University, MS. Samples were collected on weekends in which the Ole Miss Rebel football team held home games (Vaught-Hemingway Stadium, University, MS 38677). The collected samples were analyzed using a validated method and found to contain Amp, Meth, MDMA, Coc and BE. The concentrations of Amp and BE significantly rose in the university wastewater during football games.


PubMed | Elsohly Laboratories, Inc. and University of Mississippi
Type: Journal Article | Journal: Journal of analytical toxicology | Year: 2016

Continuing our previous studies analyzing drugs of abuse in municipal wastewater, a method was developed for the analysis of opiates in wastewater samples using liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). Eight opiate drugs and metabolites were analyzed including codeine, hydrocodone, hydromorphone, 6-monoacetylmorphine (6-MAM, the primary urinary metabolite of heroin), morphine, norhydrocodone (the primary urinary metabolite of hydrocodone), oxycodone and oxymorphone. These drugs were chosen because of their widespread abuse. Wastewater samples were collected at both the Oxford Waste Water Treatment Plant in Oxford, Mississippi (MS) and the University Wastewater Treatment Plant in University, MS. These wastewater samples were collected on weekends in which the Ole Miss Rebel football team held home games (Vaught-Hemingway Stadium, University, MS 38677). The collected samples were analyzed using a validated method and found to contain codeine, hydrocodone, hydromorphone, morphine, norhydrocodone, oxycodone and oxymorphone. None of the samples contained 6-MAM.


PubMed | Elsohly Laboratories, Inc. and University of Mississippi
Type: Journal Article | Journal: Drug development and industrial pharmacy | Year: 2016

Cannabinoids are increasingly being used in the treatment of chemotherapy-induced nausea and vomiting (CINV) because of their action on the cannabinoid receptors, CB1 and CB2. The currently marketed capsule formulations (sesame oil based and crystalline powder) are required to be administered frequently to maintain therapeutic levels, which leads to non-compliance. In the present study, oral controlled release tablet formulations of (9)-tetrahydrocannabinol (THC) were prepared using the lipids Precirol and Compritol. Release profiles using THC-lipid matrices and/or with the lipids in the external phase (blend) were evaluated. The effect of directly compressible diluents lactose mixture (Ludipress), dicalcium phosphate anhydrous (Emcompress) and microcrystalline cellulose (Avicel 102) on tablet characteristics and in vitro drug release was also investigated. Further, in vitro THC release in the presence of a lipase inhibitor, Pluronic F68, was also studied. A 24 h zero-order THC release profile was obtained with a combination of Precirol and Compritol in the compression blend. Addition of Pluronic F68 did not alter THC release in vitro. These optimized tablets were chemically and physically stable for 3 months, the last time point tested, at 25C/60% RH. The overall results demonstrate the feasibility of preparing oral THC tablets for once a day administration which can improve CINV management.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 167.38K | Year: 2011

DESCRIPTION (provided by applicant): Currently, FDA approved clinical applications of 9-Tetrahydrocannabinol (THC) include control of nausea and vomiting associated with chemotherapy and for appetite stimulation for AIDS patients suffering from anorexia and wasting syndrome. However, THC also has significant potential in the treatment of glaucoma, the second largest cause of blindness, by decreasing intraocular pressure and by acting as a retinal neuroprotectant, through an interaction with the cannabinoid receptors expressed on the ocular tissues. To date, however, lack of an appropriate mechanism for effective topical delivery of THC has been a limiting factor. We propose to broaden the paradigm of THC research to appropriate drug design and deliverystrategies to enhance ocular bioavailability, through topical administration, of this valuable medicinal compound. This project will test the hypothesis that selected novel hydrophilic amino acid (AA), dicarboxylic acid (DCA) or combination (AA-AA, AA-DCA)based THC prodrugs will improve transcorneal penetration and will demonstrate optimal resistance to enzymatic and chemical hydrolysis. Our approach in Aim 1 will be to select and synthesize THC prodrugs and their salts. Specifically, amino and/or dicarboxylic acids will be linked to THC in a manner to yield THC prodrugs (THC-AA, THC-AA-AA, THC-DCA, and THC-AA-DCA) representing a variety of computed logP values, charge and chain length and their salts. The identity of the prodrugs synthesized will be established using analytical tools such as HPLC-MS and NMR (1H and 13C). Under Aim 2, physicochemical characteristics, aqueous solubility, pH dependent solubility and stability in aqueous solutions, as well as bioreversion of the prodrugs in ocular tissue homogenates and aqueous and vitreous humor will be determined. In vitro permeability will be evaluated using isolated rabbit corneas. Finally, Aim 3 will determine ocular bioavailability and pharmacological activity of selected THC prodrugs in vivo in New Zealand albino rabbits. Intraocular pressure (IOP) lowering properties of the selected prodrugs will be compared to that of the parent drug, THC. Suitable formulations for topical delivery will be prepared. In addition to evaluating the effect on the IOP, ocularbioavailability of the most effective prodrug/dose will be determined in the anesthetized rabbit model using a dual probe ocular microdialysis technique to sample the aqueous and vitreous humor. Plasma THC levels, as well as THC acid and 11-hydroxy THC metabolite levels, at the final time point, will also be determined in these studies to estimate systemic exposure. It is expected that the innovative THC prodrugs proposed in this application will be markedly more hydrophilic and stable, compared to THC, and will show significant IOP lowering activity following topical application. Additionally, this study will provide a better understanding of the physicochemical and formulation characteristics necessary for drug penetration into the back-of-the eye tissuesfollowing topical administration and thus help improve treatment options for glaucoma as well as a host of other ocular diseases. PUBLIC HEALTH RELEVANCE: This STTR Phase I application is directed towards the development of hydrophilic tetrahydrocannabinol (THC) prodrugs for topical administration as eyedrops. Such prodrugs will be of great value in the prevention of loss or deterioration of vision in patients suffering from glaucoma.

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