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Adulterants and substitutes.

The presence of an adulterant in an already inherently toxic street drug leaves both the user and the emergency physician with a harsh predicament. Both may be in the dark as to the true nature of the active ingredients, or as to the clinical effects produced by these substances or combinations of substances. This creates a diagnostic and therapeutic dilemma for the treating physician, as he or she wrestles with the often contradictory clinical signals and the inescapable possibility that prescribed therapy may interact adversely with the compounds already exerting their effects. The only defense we have is an open and constantly probing thought process, which maintains an awareness of the current street drug culture, and then channels this information into the clinical decision process.

Adult↗

Risks associated with herbal medicinal products.

Health risks associated with the use of herbal medicinal products (HMPs) are often an emotionally discussed issue. The topic is, however, important not least because of the present popularity of HMPs. This article aims to provide a factual overview of this complex subject. The evidence relating to the toxicity, interactions and quality of a number of HMPs is reviewed. Toxicity data indicate that some HMPs have the potential to cause serious adverse events and fatalities. HMPs affect pharmacokinetic and pharmacodynamic factors and thus cause herb-drug interactions. Reports of HMPs affected by contamination, adulteration or substitution of botanical material have repeatedly caused concern. Asian HMPs are most often implicated. It is concluded that HMPs are not free of risk. More research and more information are required in order to maximize consumers' safety.

Drug Contamination↗

Performance evaluation of three on-site adulterant detection devices for urine specimens.

The performance of three on-site adulterant detection devices that assess the integrity of urine specimens collected for drug-of-abuse testing was evaluated: the Intect 7, MASK Ultra Screen, and Adultacheck 4. Intect 7 simultaneously tests creatinine, nitrite, glutaraldehyde, pH, specific gravity, and the presence of bleach and pyridinium chlorochromate (PCC). Mask Ultra Screen tests creatinine, nitrite, pH, specific gravity, and oxidants, and Adultacheck 4 tests creatinine, nitrite, glutaraldehyde, and pH. Urine specimens were prepared with the Substance Abuse and Mental Health Administration regulated analytes at 50% above the cut-off concentrations. Stealth, Urine Luck, Instant Clean ADD-IT-ive, and KLEAR were added individually to the drug-added urine specimens so that their concentrations reflected the "optimum" usage reported in their package inserts and 25% above and below that optimum. Stealth is reported to be peroxidase; Urine Luck is believed to be PCC; Instant Clean ADD-it-ive reportedly contains glutaraldehyde, and Klear is a nitrite. The following diluents/adulterants were added at 25%, 33%, and 50% of the volume of drug-added urine: distilled water, bleach, ammonia, and vinegar. Of the devices tested, Intect 7 proved to be the most sensitive, and it correctly indicated the presence of adulterant or diluent in all samples tested. In order to do so, all indication pads had to be assessed in concert. Adultacheck 4 specifically assesses four characteristics of urine integrity and is therefore very limited in detecting the use of several popular adulterants that are commercially available. Although it correctly assessed the four characteristics, it did not detect the use of Stealth, Urine Luck, or Instant Clean ADD-it-ive. Mask Ultra Screen can potentially detect a broader range of adulterants than Adultacheck 4. However, in practice, it only detected them at levels well above their optimum usage, making it less efficacious than Intect 7. Clearly, the specific identification of an adulterant is a trade-off for sensitive detection of several adulterants.

Drug Contamination↗

Potassium nitrite reaction with 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in urine in relation to the drug screening analysis.

Recently potassium nitrite has been used as an adulterant to interfere with the analysis of 11-nor-delta 9-tetrahydro-cannabinol-9-carboxylic acid (THC-COOH) in urine. A comprehensive study of the THC-COOH and nitrite reaction chemistry and stability under various conditions is presented. Reverse phase high performance liquid chromatography (HPLC) and negative electrospray mass spectrometry (ESMS) results are given to substantiate the derived reaction mechanism and properties leading to reaction termination. The addition of potassium carbonate as a buffering agent prior to or following sample void as a means of preventing the formation of a nitroso-complexed form of the 11-nor-delta 9+-tetrahydrocannabinol-9-carboxylic acid is evaluated.

Carbonates↗

The development of addiction to d-amphetamine in an animal model: same principles as for alcohol and opiate.

We have established a rat model that reflects the course of development of alcohol and opiate addiction. The present study with d-amphetamine aimed to define general principles in the development of an addiction. Male rats had a continuous free choice between d-amphetamine solutions (100, 200 and 400 mg/l) and water for 47 weeks. An initial intake of high doses of d-amphetamine during the first weeks of drug choice was followed by an individually stable pattern of drug consumption of moderate drug doses. During this period of controlled consumption (from week 10 to week 40), the voluntary intake of d-amphetamine depended on individual factors (dominant rats: 0.37+/-0.02 mg/kg per day, subordinate rats: 0.57+/-0.05 mg/kg per day) and environmental variables (group housing: 0.21+/-0.02 mg/kg per day, single housing: 0.41+/-0.03 mg/kg per day). Beginning with week 41, voluntary d-amphetamine consumption progressively increased (1.9+/-0.2 mg/kg per day in week 47), although the experimental conditions remained unchanged. Drug intake during a retest (free choice as before) after 6 months of drug deprivation revealed that the rats had persistently lost their control over drug intake and were no longer able to adjust drug taking to internal and external conditions. These addicted rats took very high drug doses, even when all d-amphetamine solutions but not water were adulterated with bitter tasting quinine (6.6+/-0.6 mg/kg per day; age-matched controls: 0.37+/-0.04 mg/kg per day). Forced intake of d-amphetamine for 47 weeks (7.1+/-0.3 mg/kg per day) via the drinking fluid caused physical dependence (hyperreactivity during withdrawal) but did not lead to drug addiction (voluntary intake in the retest with adulteration: 0.42+/-0.04 mg/kg per day). Both the temporal development and the prerequisites of psychostimulant addiction were in principle the same as for alcohol and opiates.

Animals↗

The medical review officer.

The role and responsibilities of the medical review officer are considered in relation to drug testing in the workplace. Knowledge of substance abuse disorders, pharmacology and toxicology, laboratory techniques for screening and confirmation, forensic collection techniques, and the relevant rules and regulations that govern drug testing is essential. The means for detecting adulterated urine samples are offered, and a procedure for the management of urine-testing results is provided.

Environment↗

Determination of Cry9C protein in processed foods made with StarLink corn.

StarLink (Aventis CropScience US) hybrid corn has been genetically modified to contain a pesticidal protein, Cry9C, which makes it more resistant than traditional varieties to certain types of corn insect pests. Unlike other varieties of genetically engineered corn, the U.S. Environmental Protection Agency authorized the use of StarLink corn for animal feed and industrial use only, not for human consumption. However, some Cry9C-containing corn was mistakenly or inadvertently comingled with yellow corn intended for human food use. Because corn containing the Cry9C construct was not approved for human use, the U.S. Food and Drug Administration considers food containing it to be adulterated. Consequently, this regulatory violation resulted in hundreds of recalls of corn-based products, such as taco shells, containing cry9C DNA. Detecting the novel protein in StarLink corn is an emerging issue; therefore, there is no standardized or established analytical method for detecting Cry9C protein in processed foods. We developed a procedure for quantitation of Cry9C protein, with validation data, in processed food matrixes with a limit of quantitation at 1.7 ng/g (ppb), using a commercial polyclonal antibody-based Cry9C kit that was intended for corn grain samples. Intra- and interassay coefficients of variation were 2.8 and 11.8%, respectively. Mean recoveries were 73 and 85% at 2 and 5 ng/g Cry9C fortifications, respectively, for 19 control non-StarLink corn-based matrixes. Our data demonstrate only 0-0.5% of Cry9C protein survived the processing of tortilla chips and soft tortillas made from 100% StarLink corn, resulting in levels from below the detection limit to 45 ppb.

Bacillus thuringiensis Toxins↗

Regulation of drugs and chemicals used by the poultry industry. Good manufacturing practices.

Good manufacturing practices (GMP) are required to be followed in the use of animal drugs to produce medicated feeds. The authority is found in the federal Food, Drug, and Cosmetic Act, which states that medicated feed can be deemed adulterated if GMP were not followed in its production. This authority has been translated into GMP regulations applicable to all medicated feed production. More detailed GMP are imposed on those using high potency sources of drugs that require a withdrawal period (Category II). Less detailed GMP are imposed on all other drug uses (Category I and lower potency sources of Category II). Facility registration, medicated feed applications, and biennial inspections are also imposed on those required to follow the more detailed GMP regulations. The basic thrust of the regulations is assurance that drug use is correct in all respects and that the integrity of all medicated and nonmedicated feeds is maintained. The objective is food free of illegal drug residues, i.e., food safety. The GMP regulations are based on joint industry-government endeavor and reflect the practical realities of feed manufacturing. They are, for all practical purposes, good business practices assuring that medicated feeds make a positive contribution to food production and consumer confidence.

Animals↗

Determination of lidocaine in hair of drug fatalities by headspace solid-phase microextraction.

The local anesthetic lidocaine was determined in hair by hydrolysis of the samples with 4% NaOH in the presence of excessive Na2SO4 and subsequent headspace solid-phase microextraction with a 65-microm Carbowax/divinylbenzene fiber, and gas chromatography-mass spectrometry measurement with etidocaine as the internal standard. The calibration curve was linear between 0.1 and 1000 ng/mg. The detection and quantitation limits were 0.1 and 0.4 ng/mg, respectively. The method was applied to hair samples of 49 drug fatalities, and positive results were obtained in 32 cases with lidocaine concentrations between 0.4 and 400 ng/mg and 675 ng/mg in one extreme case. For comparison, morphine, 6-acetylmorphine, codeine, dihydrocodeine, methadone, cocaine, and benzoylecgonine were also determined by usual methods. From segmental investigations in four of the cases and from comparison with the hair concentrations of the other drugs, it follows that lidocaine was consumed for a longer period of time as an adulterant of cocaine and heroin preparations.

Adolescent↗

Federal regulation: philosophy and practice.

The philosophy of drug regulation as expressed by Congress has progressively embraced concepts of misbranding and adulteration, safety, efficacy, and, most recently, control of the investigational process. The intent of Congress has been implemented by a series of regulations intended to protect the public health and to assure that available drugs are safe and effective. This has resulted in more centralized, standardized, uniform government control, with a slowdown in the development and approval of new drugs, an increase in the cost of developing and marketing new drugs, and costly control procedures. It is time to ask whether the benefit of more centralized government control is being exceeded by its cost.

Clinical Trials as Topic↗

Acquired preference for morphine but no d-amphetamine as a result of saccharine adulteration.

Consumption of morphine sulfate and d-amphetamine was studied in two groups of rats. In a choice situation, preference for both drugs remained low after 46 days of drinking. In two additional groups morphine and d-amphetamine solutions were prepared with 1% saccharine. Morphine drinking was significantly increased by saccharine adulteration, whereas drinking of amphetamine solutions decreased. Addition of saccharine to morphine solutions increased drinking in more than a simple additive way. Saccharine facilitates the acquisition of drug-directed behavior. The slope of the acquisition trials for the morphine-saccharine group was significantly different from horizontal (O-slope) and significantly different from the slope found for the morphine without saccharine group.

Animals↗