David E Moody

• Ph.D.
• Managing Director at University of Utah

Background Buprenorphine is a common analgesic administered to rabbits and high concentration formulations can reduce handling stress without sacrificing pain relief. The objective of this study was to evaluate the pharmacokinetics of high concentration buprenorphine and its metabolites following multiple subcutaneous doses in the rabbit. Laborator...

Neonates experience dramatic changes in the disposition of drugs after birth due to enzyme maturation and environmental adjustment, challenging therapeutic decision making. In this research, we establish postnatal age, postmenstrual age, and body weight as physiologically reasonable predictors of morphine's clearance in neonates. By integrating kno...

Neonatal abstinence syndrome (NAS) is a condition affecting newborns that are exposed to an opioid in utero. In a randomized, controlled trial assessing the efficacy of buprenorphine and morphine in NAS, blood samples were analyzed from a subset of patients receiving buprenorphine along with NAS scores. The data were used to validate and adapt an e...

Objective Neonatal abstinence syndrome (NAS)—a clinical entity of infants from in utero exposure to psychoactive xenobiotic and buprenorphine—has been successfully used to treat NAS. However, nothing is known about the pharmacokinetics (PK) of buprenorphine in neonates with NAS. To our knowledge, this is the first study to investigate the populatio...

Opioid-related mortality rates have escalated. Drug interactions may increase blood concentrations of the opioid. We therefore used human liver microsomes (HLMs) and cDNA-expressed human cytochrome P450s (rCYPs) to study in vitro inhibition of buprenorphine metabolism to norbuprenorphine (CYP3A4 and 2C8), oxycodone metabolism to noroxycodone (CYP3A...

Cocaine decreases methadone and buprenorphine plasma concentrations. HIV infection and/or antiretroviral medication use may impact these relationships. We sought to determine the association between recent cocaine use and methadone and buprenorphine concentrations in HIV-infected and uninfected subjects in clinical care. R- and S-methadone or bupre...

Abstract Cocaine use disorders are mediated by the cocaine blockade of the dopamine transporter in the central nervous system (CNS). On the basis of the concept that these effects could be obviated if cocaine were prevented from reaching its cognate receptors in the CNS, we have developed an anticocaine vaccine, dAd5GNE, based on a cocaine analog c...

The purpose of this study was to examine the effect of hepatitis C virus (HCV) infection on buprenorphine pharmacokinetics in opioid-dependent, buprenorphine/naloxone-maintained adults. A retrospective analysis of buprenorphine pharmacokinetics in HCV seropositive and seronegative buprenorphine/naloxone-maintained individuals (N = 49) was undertake...

In vitro inhibition of oxycodone metabolism to noroxycodone and oxymorphone and R- and S-methadone metabolism to R- and S-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) was measured for four H2-receptor antagonists and five proton-pump inhibitors (PPIs) using human liver microsomes (HLM) and cDNA-expressed human cytochrome P450s (rCYPs)....

The opioid analgesic oxycodone is widely abused and increasingly associated with overdose deaths. A sensitive analytical method was developed for oxycodone and its metabolites, noroxycodone and oxymorphone, in human plasma, urine (±enzymatic hydrolysis at 50°C for 16 h) and liver microsomes (HLMs). Liquid–liquid extraction was followed by high-perf...

Global access to opioid agonist therapy and HIV/hepatitis C virus (HCV) treatment is expanding but when used concurrently, problematic pharmacokinetic and pharmacodynamic interactions may occur. Articles published from 1966 to 2012 in Medline were reviewed using the following keywords: HIV, AIDS, HIV therapy, HCV, HCV therapy, antiretroviral therap...

Buprenorphine is the cornerstone of pain management in nonhuman primates, but the pharmacokinetics of this widely used drug are unknown. The purpose of this study was to evaluate the pharmacokinetic profiles of buprenorphine (0.01 and 0.03 mg/kg IM) and sustained-release buprenorphine (0.2 mg/kg SC) in 2 macaque species (M. mulatta and M. fascicula...

Introduction: Methadone and buprenorphine are maintenance replacement therapies for opioid dependence; they are also used for pain management. Methadone and buprenorphine (to a lesser extent) have seen sharp increases in mortality associated with their use. They have distinct routes of metabolism (mostly cytochrome P450 dependent), and distinct ph...

Background: Interactions between human immuno-deficiency virus (HIV) and opioid-dependence therapies can occur. Objectives: We sought to determine whether such interactions occurred between buprenorphine/naloxone and raltegravir. Methods: We performed a within-subject open-labeled pharmacokinetic and pharmacodynamic study in 12 HIV-seronegativ...

The benzodiazepines are a class of a relatively large number of drugs that share a common chemical structure and have anxiolytic to sedative action on the central nervous system (CNS). They are chemically diverse, but share a classic structure that consists of a benzene fused to a seven-membered diazepine ring. Benzodiazepines are noted to have bot...

Patterns of buprenorphine and metabolites were examined in 1946 positive urine samples analyzed by liquid chromatography-tandem mass spectrometry for free (unconjugated) buprenorphine and norbuprenorphine (quantitative, 2 to 1000 ng/mL) and buprenorphine-glucuronide (B3G) and norbuprenorphine-glucuronide (N3G) (semi-quantitative, 5 to 1000 ng/mL)....

This study examined drug interactions between buprenorphine, a partial opioid agonist used for opioid dependence treatment and pain management, and the protease inhibitors (PIs) darunavir-ritonavir and fosamprenavir-ritonavir. The pharmacokinetics of buprenorphine and its metabolites and symptoms of opioid withdrawal or excess were compared in opio...

The only medication used sublingually in the neonate is buprenorphine for the treatment of neonatal abstinence syndrome (NAS). Compared with morphine, buprenorphine reduces the length of treatment and length of hospitalization in neonates treated for NAS. The objective of this study was to characterize the stability of ethanolic buprenorphine for s...

Prescription opioid misuse and unintentional overdose deaths involving these analgesics are increasing public health concerns among all ages in the United States.1-4 According to the US Centers for Disease Control and Prevention, prescription opioid-related overdose deaths have become the leading cause of injury deaths, outpacing motor-vehicle cras...

This series of studies examines the pharmacokinetic/pharmacodynamic interactions between buprenorphine, an opioid partial agonist increasingly used in treatment of opioid dependence, and rifampin, a medication used as a first line treatment for tuberculosis; or rifabutin, an alternative antituberculosis medication. Opioid-dependent individuals on s...

Gender differences are known to occur in the pharmacokinetics of many drugs. Mechanisms may include differences in body composition, body weight, cardiac output, hormonal status, and use of different co-medications. Recently subtle gender-dependent differences in cytochrome P450 (CYP) 3A-dependent metabolism have been demonstrated. Buprenorphine N-...

Sublingual buprenorphine and buprenorphine/naloxone are efficacious opioid dependence pharmacotherapies, but there are reports of their diversion and misuse by the intranasal route. The study objectives were to characterize and compare their intranasal pharmacodynamic and pharmacokinetic profiles. A randomized, double-blind, placebo-controlled, cro...

Previous reports on the pharmacokinetic of tipranavir (TPV) and buprenorphine (BUP)/ naloxone found that coadministration resulted in an 80% reduction in the area under the curve AUC of the primary BUP metabolite, norBUP, without any pharmacodynamic consequences. This study was conducted to characterize how tipranivir/ritonavir effects the glucuron...

In vitro metabolism of methadone was investigated in cytochrome P450 (CYP) supersomes and phenotyped human liver microsomes (HLMs) to reconcile past findings on CYP involvement in stereo-selective metabolism of methadone. Racaemic methadone was used for incubations; (R)- and (S)-methadone turnover and (R)- and (S)-EDDP formation were determined usi...

This study was conducted to examine the pharmacokinetic interactions between buprenorphine/naloxone (BUP/NLX) and lopinavir/ritonavir (LPV/r) in HIV-seronegative subjects chronically maintained on BUP/NLX. This study was an open labeled pharmacokinetic study in twelve HIV-seronegative subjects stabilized on at least 3 weeks of BUP/NLX therapy. Subj...

To improve outcomes among injection drug users with HIV and/or chronic hepatitis B, it is important to identify drug interactions between antiretroviral and opiate therapies. We report the results of a study designed to examine the interaction between buprenorphine and the nucleos(t)ide reverse transcriptase inhibitors (NRTI) didanosine (ddI), lami...

The effect of chronic cocaine use on buprenorphine pharmacokinetics was investigated to identify drug interactions and potential toxicities. In a retrospective analysis, pharmacokinetics were compared for 16 studies completed on subjects who were regular cocaine users and 74 studies on subjects who used cocaine only occasionally or not at all. All...

This study was conducted to determine whether drug interactions of clinical importance occur between buprenorphine, an opioid partial agonist medication used in treatment of opioid dependence, and the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine. Opioid-dependent, buprenorphine/naloxone-maintained, HIV-negative volunteers (n = 7...

HIV-infected patients with opioid dependence often require opioid replacement therapy. Pharmacokinetic interactions between HIV therapy and opioid dependence treatment medications can occur.HIV-seronegative subjects stabilized on at least 3 weeks of buprenorphine/naloxone (BUP/NLX) therapy sequentially underwent baseline and steady-state pharmacoki...

A highly sensitive method was developed to measure naloxone and its metabolite nornaloxone in human plasma, urine, and human liver microsomes (HLM). Naltrexone-d(3) and oxymorphone-d(3) were used as respective internal standards. Solid-phase extraction, using mixed mode extraction columns and 0.1 M phosphate buffer (pH 5.9), was combined with high-...

We tested the hypothesis that primary cultures of human hepatocytes could predict potential drug interactions with methadone and buprenorphine. Hepatocytes (five donors) were preincubated with dimethyl sulfoxide (DMSO) (vehicle), rifampin, or nelfinavir before incubation with methadone or buprenorphine. Culture media (0-60 min) was analyzed by liqu...

Cocaine withdrawal symptoms are thought to play a role in relapse; studies characterizing the symptomatology have yielded mixed findings. This study sought to examine the pharmacodynamic/pharmacokinetic profile of repeated high dose exposure to oral cocaine and characterize acute and protracted withdrawal in cocaine abusers. This study employed a r...

Gamma-vinyl-gamma-aminobutyric acid (GVG) elevates central nervous system gamma-aminobutyric acid (GABA) levels by irreversibly inhibiting GABA transaminase. An open-label clinical trial in humans suggested that GVG may reduce cocaine and methamphetamine use. To test safety and to obtain preliminary data on efficacy of GVG for treating methamphetam...

Buprenorphine metabolism was recently expanded by in vitro identification of a number of hydroxylated metabolites. The identification of two, M1 and M3, in urine suggests that they may be quantitatively significant metabolites. To further understand the in vivo regulation of this mode of metabolism, we evaluated 24-hr urine from subjects (10 per tr...

A rugged liquid chromatographic-electrospray ionization-tandem mass spectrometric (LC-ESI-MS-MS) method was developed and validated for accurate monitoring of steady-state plasma aripiprazole. Haloperidol-d(4) was chosen as the internal standard. ESI of aripiprazole and haloperidol-d(4) yielded abundant MH(+) ions, m/z 448 and 379, respectively. Th...

We investigated the enzyme kinetics of buprenorphine and norbuprenorphine glucuronidation in human liver microsomes and UDP-glucuronosyltransferase (UGT) Supersomes. The involvement of UGT 1A1, 1A3 and 2B7 in buprenorpine and 1A3 in norbuprenorphine glucuronidation were confirmed. Novel involvement of 2B17 with buprenorphine and 1A1 with norbupreno...

In utero exposure to drugs of abuse can lead to neonatal abstinence syndrome, a condition that is associated with prolonged hospitalization. Buprenorphine is a partial mu-opioid agonist used for treatment of adult detoxification and maintenance but has never been administered to neonates with opioid abstinence syndrome. The primary objective of thi...

A liquid chromatography-electrospray ionization-tandem mass spectrometry method has been developed and validated to detect (R)- and (S)-methadone and (R)- and (S)-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in human plasma with cross-validation to urine and liver microsomes. Use of deuterated internal standards and liquid-liquid extrac...

Pharmacokinetic analysis of buprenorphine administered to six healthy dogs via the oral transmucosal (OTM) route at doses of 20 and 120 microg/kg was conducted using liquid chromatography-electrospray ionization-tandem mass spectroscopy (LC-ESI-MS/MS). Bioavailability was 38% plus or minus 12% for the 20 microg/kg dose and 47%+/-16% for the 120 mic...

Opioid addiction and HIV disease frequently co-occur. Adverse drug interactions have been reported between methadone and some HIV medications, but less is known about interactions between buprenorphine, an opioid partial agonist used to treat opioid dependence, and HIV therapeutics. This study examined drug interactions between buprenorphine and th...

To improve the analysis of naltrexone and its primary metabolite 6beta-naltrexol, a sensitive and specific method for the analysis of subnanogram-per-milliliter concentrations of these analytes in human, rat, and rabbit plasma was developed utilizing liquid chromatography (LC) coupled to electrospray ionization (ESI) tandem mass spectrometry (MS-MS...

Although buprenorphine is approved for use in the outpatient treatment of opioid addiction in 2 tablet formulations, a monoproduct containing buprenorphine only (Subutex) and a buprenorphine/naloxone combination product (Suboxone), much of the clinical data that support the approval by the U.S. Food and Drug Administration were generated by using a...

The availability of buprenorphine (BUP) provides an alternative approach to the treatment of opioid addiction with methadone, an agent that has many drug-drug interactions when combined with antiretroviral therapy (ART). However, due to limited long-term pharmacokinetic studies in HIV-infected patients, the clinical use of BUP, a CYP450-3A4 substra...

Buprenorphine (BUP) is effective in the treatment of opioid dependence when given on alternating days, probably as a result of long-lasting occupation of micro opioid receptors (microORs). This study examined the duration of action of BUP at microORs and correlations with pharmacokinetic and pharmacodynamic outcomes in 10 heroin-dependent volunteer...

Buprenorphine is used for the treatment of opioid dependence. As the number of persons receiving buprenorphine treatment and antiretroviral therapy continues to grow, so too does the existence and clinical impact of drug interactions between buprenorphine and medications for treating human immunodeficiency virus (HIV) infection. Awareness that such...

We examined drug interactions between buprenorphine, an opioid partial agonist available by prescription for treatment of opioid dependence, and the protease inhibitors (PIs) nelfinavir (NFV), ritonavir (RTV), and lopinavir/ritonavir (LPV/R). Opioid-dependent, buprenorphine/naloxone-maintained, human immunodeficiency virus (HIV)-negative volunteers...

This study examined drug interactions between buprenorphine, an opioid partial agonist medication used in the treatment of opioid dependence, and the nonnucleoside reverse-transcriptase inhibitors (NNRTIs) efavirenz (EFV) and delavirdine (DLV). Opioid-dependent, buprenorphine/naloxone-maintained, human immunodeficiency virus (HIV)-negative voluntee...

Forensic toxicology encompasses the determination of the presence and concentration of drugs, other xenobiotics and their metabolites in physiological fluids and organs and the interpretation of these findings as they may impact on legal issues. These include medical examiner investigations, driving under the influence and other transportation acci...

The opioid partial agonist medication, buprenorphine (BUP), and its primary metabolite, norbuprenorphine (NBUP), are extensively glucuronidated. Sensitive analytical methods that include determination of buprenorphine-3-glucuronide (BUPG) and norbuprenorphine-3-glucuronide (NBUPG) are needed to more fully understand the metabolism and pharmacokinet...

Aim: Buprenorphine is an effective medication for treatment of opioid dependence. An injectable depot formulation of buprenorphine has been developed using biodegradable polymer microcapsule technology. This formulation may offer effective treatment of opioid dependence and enhance treatment delivery while minimizing risks of patient non-adherence...

The in vitro metabolism of buprenorphine was investigated to explore new metabolic pathways and identify the cytochromes P450 (P450s) responsible for the formation of these metabolites. The resulting metabolites were identified by liquid chromatography-electrospray ionization-tandem mass spectrometry. In addition to norbuprenorphine, two hydroxylat...

Two tablet formulations of buprenorphine (a buprenorphine mono-product, Subutex, and a buprenorphine/naloxone combination product, Suboxone) are available for use in the treatment of opioid addiction; however, the bulk of the clinical studies supporting its approval by the US Food and Drug Administration (FDA) were conducted with a sublingual liqui...

Buprenorphine is an effective medication for treatment of opioid dependence. An injectable depot formulation of buprenorphine has been developed using biodegradable polymer microcapsule technology. This formulation may offer effective treatment of opioid dependence and enhance treatment delivery while minimizing risks of patient non-adherence or il...

This study compared the ability of two on-site testing devices, Instant-View Test Card and OnTrak TesTcup Pro 5, to discriminate negative from positive urine samples for cannabinoids, cocaine metabolite, opiates, amphetamines, and benzodiazepines. The on-site devices were evaluated in a precision study with fortified urine samples and in a clinical...

We evaluated peak plasma concentrations, trough concentrations, and the 24-hour area under the concentration curve (AUC(0-24 h)) during maintenance with sublingual (SL) liquid or tablet formulations in 57 opiate-dependent volunteers. Study participants were assigned randomly to one of three SL daily buprenorphine dose pairs and maintained for 2 wee...

This is the first trial to compare the relationship of opioid plasma concentrations in methadone-versus buprenorphine-maintained subjects. Sixty subjects (19 females and 41 males) seeking treatment who met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for opioid dependence were recruited and treated at the Drug Addiction Outpatient...

A simple method, exposure to natural-light, was developed to remove riboflavin from urine to enhance its use as the biological matrix for the preparation of calibration and control samples. Riboflavin-depleted urine containing less than 1 ng/ml of riboflavin was used to validate a high-performance liquid chromatography with fluorescence detection m...

Nalmefene is an opioid antagonist used in the treatment of alcoholism and opioid overdose. A highly sensitive method was developed to measure nalmefene in human and rabbit plasma and rabbit serum. Nalbuphine was used as internal standard. Liquid-liquid extraction was applied using n-butyl chloride/acetonitrile (4:1). High-performance liquid chromat...

To determine whether enzyme inhibition explains the clinical adverse interaction of benzodiazepines and buprenorphine. Buprenorphine was incubated in the presence of benzodiazepines (or metabolites) with human liver microsomes (HLMs). A number of benzodiazepines were screened at therapeutic concentrations after 0-min and 15-min preincubation times....

Quetiapine is an atypical antipsychotic agent for the treatment of schizophrenia. After an oral dose it is absorbed rapidly and extensively metabolized in the liver, resulting in low plasma concentrations of the parent drug. A sensitive analytical method is needed. A liquid chromatographic-electrospray-tandem mass spectrometric (LC-ESI-MS-MS) metho...

Risperidone, a benzisoxazole derivative, is an antipsychotic agent used for the treatment of schizophrenia. We developed a liquid chromatographic-atmospheric pressure chemical ionization-tandem mass spectrometric (LC-APCI-MS-MS) method with improved sensitivity, selectivity, and dynamic range for determination of risperidone and 9-hydroxyrisperidon...

Levo-acetyl-alpha-methadol (LAAM) exerts most of it mu-agonist activity through the action of its 2 N-demethylation metabolites, norLAAM and dinorLAAM. The N-demethylation of LAAM to norLAAM and norLAAM to dinorLAAM is primarily performed by cytochrome P450s (CYP) in the 3A family. No previous studies have been conducted to determine the effect of...

Buprenorphine is an approved medication for the treatment of opioid dependence. Three sublingual formulations have been used at various times during its development-a solution containing alcohol, tablets containing buprenorphine alone, and tablets containing buprenorphine plus naloxone. This study compared the relative buprenorphine bioavailability...

Immunoassays are commonly used to screen samples prior to confirmation by gas chromatography-mass spectrometry (GC-MS). This serves two purposes: it provides a second method for positive samples, and it allows exclusion of negative samples from further confirmatory testing. In addition, immunoassay results can be used in some cases to determine if...

The purpose of this chapter is to examine the drug interactions that occur with benzodiazepines and discuss the relevance of these interactions to the field of medicine in general with an emphasis on forensic toxicology. Because of the diverse nature of the benzodiazepines, some time has been taken to introduce this class of drugs. This introductor...

The clinical effectiveness of opioid maintenance for heroin dependence is believed to result from a medication's ability to decrease mu-opioid receptor (muOR) availability thereby replacing agonist effects, alleviating withdrawal symptoms and attenuating heroin effects. We empirically tested this hypothesis in five heroin-dependent volunteers who w...

An effective method for the determination of gamma-hydroxybutyric acid (GHB) in human plasma is described that utilizes a simple liquid-liquid extraction procedure and gas chromatography-positive ion chemical ionization-mass spectrometry (GC-PCI-MS). The method has been used to study the stability of plasma GHB under several storage conditions. Fol...

Gas chromatography/mass spectrometry (GC/MS) is often used for detection and measurement of cocaine metabolites in biological specimens. However, cocaine N-oxide, a recently identified metabolite of cocaine, is thermally degraded when introduced into a GC/MS. The major degradation products are cocaine and norcocaine. When cocaine N-oxide was measur...

Capsaicin is a common dietary constituent and a popular homeopathic treatment for chronic pain. Exposure to capsaicin has been shown to cause various dose-dependent acute physiological responses including the sensation of burning and pain, respiratory depression, and death. In this study, the P450-dependent metabolism of capsaicin by recombinant P4...

l-Alpha-acetylmethadol (LAAM) is an alternative to methadone for the maintenance treatment of opioid dependence. LAAM has a longer therapeutic half-life than methadone, primarily because it is metabolized to more active metabolites, norLAAM and dinorLAAM. We have developed a liquid chromatography-tandem mass spectrometry method capable of measuring...

This report describes a sensitive and specific high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry method for the detection of subnanogram concentrations of selegiline and its three principle metabolites, N-desmethylselegiline, methamphetamine, and amphetamine, in human plasma. The assay has a dy...

A liquid chromatographic-electrospray ionization-tandem mass spectrometric method has been developed and validated for determination of the antiabuse medication, buprenorphine, its primary metabolite, norbuprenorphine, and a proposed coformulant, naloxone. The method uses deuterated internal standards and a simple liquid-liquid extraction. Mass spe...

Levo-alpha-acetylmethadol (LAAM) pharmacotherapy was offered to twelve patients who continued illicit opioid abuse after > or = eleven months in methadone maintenance treatment. After 6-8 weeks on LAAM, plasma concentrations of the norLAAM metabolite varied significantly by LAAM dosing day, plasma adrenocorticotropin (ACTH) concentrations were sign...

Mated Crl:CD VAF/Plus female rats, in a range-finding study (n = 5-6 per dose) and a subsequent definitive study (n = 30 per dose) were used to determine the developmental toxicity, including the teratogenic potential of levo-alpha-acetylmethadol (LAAM) hydrochloride, in tolerant rats. Tolerance was induced by initially administering the drug by ga...

In order to support studies on various medication protocols for the treatment of cocaine abuse, an accurate, precise, and sensitive (2.5 to 750 ng/mL) liquid chromatography-tandem mass spectrometry assay was developed to determine cocaine and benzoylecgonine in human plasma. Cocaine-d3 and benzoylecgonine-d3 were added as internal standards and sam...

Delta9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THCA) in human plasma can be simultaneously detected using solid-phase extraction with gas chromatography and negative ion chemical ionization mass spectrometry. THC-d3 and THCA-d3 are added as internal standards; protein is precipitated with acetonitrile and the re...

Incubation of l-α-acetylmethadol (LAAM) or norLAAM with cDNA-expressed P450s 3A4, 2B6, and 2C18 produced significant N-demethylation products. P450s 2C19, 2C8, 3A5, 2C9, 3A7, 1A1, and 2D6 (norLAAM only), also produced detectable product. Coexpression of cytochrome b5 enhanced LAAM N-demethylation, most dramatically for 3A4, but had marginal effects...

Two types of immunoassays, radioimmunoassay (RIA) and microplate enzyme immunoassay (EIA), were compared for their ability to detect and quantitate cocaine and metabolites or heroin and metabolites in extracts of sweat patches. Experiments used sweat patches that had been fortified with cocaine, benzoylecgonine (BE), and ecgonine methyl ester (EME)...

We examined three primary variables in the preparation of human liver microsomes. In three experiments, each using three livers, we manipulated 1) the force of the first centrifugation (9,000, 10,500, or 12,000g); 2) the presence of sucrose in the homogenization buffer; and 3) the number of homogenizing strokes (6, 8, or 10). Sedimentation plots fo...

Previous studies have demonstrated that the cytochrome P450 2D subfamily is involved in the 4-hydroxylation of amphetamine in the rat. These studies followed urinary levels of 4-hydroxyamphetamine and amphetamine after a single dose of amphetamine given with the P450 2D inhibitor quinidine or in P450 2D-deficient Dark Agouti (DA) rats. Multiple dos...

The cytochrome P450 (P450) 2D subfamily catalyzes ring hydroxylation of amphetamines. We tested the hypothesis that P450 2D is selectively involved in amphetamine 4-hydroxylation. Urinary elimination of 4-hydroxyamphetamine and amphetamine was determined in male Sprague-Dawley rats pretreated with P450 inducers and inhibitors. The urinary 24-h meta...

l-Alpha-acetylmethadol (LAAM) was recently approved as a substitute for methadone. LAAM, methadone, and their common metabolite, methadol, are extensively N-demethylated. The structural similarities of LAAM and its metabolites to methadone suggest that they may cross-react in methadone immunoassays. To test this hypothesis, drug-free urine was fort...

Therapeutic doses of Ritalin, a racemic mixture of d- and l-threo-methyphenidate, result in low plasma concentrations of methylphenidate. In order to assess the safety and efficacy of methylphenidate, a sensitive analytical method is needed. A gas chromatography-negative ion chemical ionization mass spectrometry (GC-NCI-MS) assay capable of measuri...

Stability is an important consideration in the use of specimens for accurate determination of analyte concentrations. To determine the long-term stability for analytes routinely analyzed by mass spectrometry in this laboratory, quality-control (QC) results were plotted versus time. The time required for the initial concentration to reach a specifie...

We examined the relative importance of G (Gi) protein-coupled brain-type (CB1-R) and spleen-type (CB2-R) cannabinoid receptors in preimplantation embryo development using agonists and antagonists specific to CB1-R and CB2-R. The results establish that endogenous cannabinoid ligands, anandamide and sn-2 arachidonoylglycerol, arrest embryo developmen...

The N-demethylation of LAAM, norLAAM, and methadone has been investigated in human liver microsomes and microsomes containing cDNA-expressed human P450s. Gas chromatography/mass spectrometry methods allowed detection of norLAAM and dinorLAAM formation from LAAM, dinorLAAM formation from norLAAM, and EDDP and EMDP formation from methadone. The rates...

Buprenorphine is used for the management of pain and has been advocated for the treatment of opioid addiction. Therapeutic doses result in low plasma concentrations of buprenorphine. In order to assess the safety and efficacy of buprenorphine, sensitive analytical methods are needed. Until recently, gas chromatography-positive ion chemical ionizati...

Solid-phase extraction (SPE) and a one-step derivatization are combined with gas chromatography-negative ion chemical ionization-mass spectrometry to simplify a previously reported method for the determination of naltrexone and its metabolite, 6-beta-naltrexol, in human plasma. Deuterated isotopomers of naltrexone and 6-beta-naltrexol are used as i...

Methadone is often invoked for detoxification and maintenance of the opioid addict. We have developed and validated a sensitive and specific method for the analysis of methadone and its metabolites, 2-ethylidene-1,5-dimethyl-3, 3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP), in human plasma, urine, and liver microsom...

Within the selective induction of phase II enzymes following treatment with dipyridyls or N-heterocyclic analogs of phenanthrene, strong correlations (r > or = 0.70) are observed between the increase of microsomal epoxide hydrolase (mEH) activity and UDP-glucuronosyltransferase (UGT) activities towards 4-nitrophenol, 1-naphthol and morphine. The pr...

We evaluated the capability of commercially available benzodiazepine immunoassays from four vendors (Abuscreen radioimmunoassay [RIA-a] from Roche Diagnostic Systems and serum RIA-d from Diagnostic Products Corporation; X-systems serum and urine fluorescence polarization immunoassays [FPIA] from Abbott Laboratories; and EMIT TOX serum and EMIT urin...