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Vitamin B2 interference with TDx drugs-of-abuse assays.

Migraine is a headache condition found in significant frequency in the general population. One recent study has shown that riboflavin, Vitamin B2, is an effective prophylactic treatment for this headache condition. One subject in a recent study conducted by the Division of Forensic Toxicology, Armed Forces Institute of Pathology (AFIP) was taking 200 mg of riboflavin twice daily for the prevention of migraine headaches. When that subject's urine was tested using Abbott TDx drugs-of-abuse assays a number of tests resulted in a MX BKG error and all samples had BLK I values greater than those observed with normal urine specimens. The MX BKG error occurs when the BLK I value is greater than the upper limit determined by the manufacturer for a particular assay. High BLK I values may result if the specimen being analyzed contains a fluorophore that will compete with the fluorescein-labeled antibody used in the assay. This error serves as a notification that an interfering substance may be present and the assay is not performing according to manufacturer-specifications. Upon termination of riboflavin therapy the subject's BLK I values began to decrease within 60 h of the last 200 mg dose. A second subject began chronic riboflavin use to confirm this interferent effect. Elevated BLK I values resulted within 3 h of a single 200 mg dose and MX BKG errors occurred 1 h after a second 400 mg dose. No false negative results were noted with either subject (both subjects used butalbital and the first subject also used hydrocodone and diazepam during the study), suggesting that riboflavin is not an adulterant. Riboflavin use, however, does interfere with the TDx DAU assays and may result in quantitative values being determined which are of questionable validity in the face of an elevated BLK I value or may result in only an MX BKG error and no quantitative value reported. It is unclear if the interfering fluorophore is simply riboflavin itself or a combination of riboflavin and its metabolic products. Results obtained on urine samples collected from individuals using prophylactic riboflavin for migraine prevention and analyzed by TDx may be of questionable validity. Such samples may require analysis utilizing another immunoassay technique that does not employ a fluorescein-labeled antibody.

Fluorescence Polarization Immunoassay↗

Analysis of illicit heroin. I. An effective thin-layer chromatographic system for separating eight opiates and five adulterants.

A thin-layer chromatographic (TLC) system with chloroform-n-hexane-triethylamine (9:9:4) as eluent that is capable of separating eight opiates and five potential adulterants, has been developed for the analysis of illicit heroin. The system was tested using illicit heroin samples and the results were confirmed by gas chromatography. The limit of detection is 0.1 microgram. Thirty-five TLC systems reported in the literature for opiate analysis were classified according to their resolving power.

Chromatography, Gas↗

Analysis and confirmation of synthetic anorexics in adulterated traditional Chinese medicines by high-performance capillary electrophoresis.

Six synthetic anorexics, clobenzorex, diethylpropion, fenfluramine, methamphetamine, phenylpropanolamine and phentermine, which can be found as adulterants in traditional Chinese medicines were assayed simultaneously by high-performance capillary electrophoresis. The electrolyte was a buffer solution containing 120 mM phosphate buffer (NaH2PO4/H3PO4, pH 2.0) and 15% acetonitrile. Applied voltage was 16 kV and temperature was 30 degrees C. Fluoren-2,7-diammonium chloride was used as an internal standard and detector set at 200 nm. The recoveries of the synthetic anorexic adulterants in traditional Chinese medicinal formula using C8-SCX mixed solid-phase extraction were studied. Several traditional Chinese medicinal powders obtained from clinics were also studied by the above HPCE method and confirmed by GC-MS. Clobenzorex, diethylpropion and fenfluramine were found and determine in these samples.

Appetite Depressants↗

Possible health and safety problems in the use of novel plant essential oils and extracts in aromatherapy.

Aromatherapy is a branch of complementary or alternative therapy which is increasing in popularity, yet has scant scientific credibility. Aromatherapy should be defined as treatment using odours and practised as such. However, essential oils are usually used in conjunction with massage and often combined with counselling of some kind. The use of most commonly-used essential oils in massage is seldom dangerous, as they have low systemic toxicity, especially when used at 2% dilution (provided they are not adulterated); however their safety during pregnancy, childbirth and babies has not been clearly demonstrated. Sensitisation, however, is a growing concern. Some aromatherapists are now introducing novel plant essential oils, extracts and phytols into their massage routine many of which have no odour and are potentially toxic. The possible dangers of these plant products are therefore discussed using specific example.

Aromatherapy↗

Noscapine as an adulterant in illicit heroin samples.

In this short report the evidence is given (based on the analyses of 22 case samples) that noscapine can be used as an adulterant in illicit heroin samples. In this context, the appearance of illicit heroin samples characterised by a high noscapine content (up to 61%) and a high noscapine/whole morphine ratio (up to 3.5) is highlighted. All samples discussed in the paper (132) were seized in Slovenia, in the period from 1997 to 1999 and were analysed by gas chromatography-mass spectrometry.

Antitussive Agents↗

[Analysis of tendency of false and inferior species from Chinese medicinal materials markets].

OBJECTIVE: To offer information on the supervision by analysing the change of origin of false and inferior species from Chinese medicinal materials (CMM) markets. METHOD: 750 cases false and inferior species from Hubei province were compared classifiedly. RESULTS: In recent ten years, distributive characteristics of false and inferior species from CMM markets is as follows. First, false and inferior species from prepared medicinal herb increase, so do with man-made adulteration and poisonous species. Second, false and inferior species increase in rural area, country fairs, individual clinics and medicine booths. Last, extracted products are sold and used as certified products. CONCLUSION: CMM country fairs, outlying rural area, individual clinics and private medicine booths are the center of further supervision hereafter.

Consumer Product Safety↗

Safety and efficacy of ginkgo (Ginkgo biloba) during pregnancy and lactation.

BACKGROUND: There is a lack of basic knowledge on the part of both clinicians and patients as to the indications for use and safety of herbal medicines used in pregnancy and lactation. This is one article in a series that systematically reviews the evidence for commonly used herbs during pregnancy and lactation. OBJECTIVES: To systematically review the literature for evidence on the use, safety, and pharmacology of ginkgo focusing on issues pertaining to pregnancy and lactation. METHODS: We searched 7 electronic databases and compiled data according to the grade of evidence found. RESULTS: There is some very weak scientific evidence from animal and in vitro studies that ginkgo leaf has antiplatelet activity, which may be of concern during labour as ginkgo use could prolong bleeding time. Low-level evidence based on expert opinion shows that ginkgo leaf may be an emmenagogue and have hormonal properties. The safety of ginkgo leaf during lactation is unknown. Patients and clinicians should be aware of past reports of ginkgo products being adulterated with colchicine. CONCLUSIONS: Ginkgo should be used with caution during pregnancy, particularly around labour where its anti-platelet properties could prolong bleeding time. During lactation the safety of ginkgo leaf is unknown and should be avoided until high quality human studies are conducted to prove its safety.

Animals↗

Kinetic determination of tight-binding impurities in enzyme inhibitors.

A novel rate equation to characterize the dose-response behavior of a moderately potent ("classical") enzyme inhibitor contaminated with a very potent ("tight-binding") impurity is derived. Mathematical properties of the new rate equation show that, for such contaminated materials, experimentally observed I(50) values are ambiguous. The four-parameter logistic equation, conventionally used to determine I(50) values, cannot be used to detect the presence of tight-binding impurities in inhibitor samples. In contrast, fitting the newly derived rate equation to inhibitor dose- response curves can, in favorable cases, reveal whether the unknown material is chemically homogeneous or whether it is contaminated with a tight-binding impurity. The limitations of our method with respect to the detectable range of inhibition constants (both classical and tight-binding) were examined by using Monte-Carlo simulations. To test the new analytical procedure experimentally, we added a small amount (0.02 mole%) of a tight-binding impurity (K(i)=0.065 nM) to an otherwise weak inhibitor of human mast-cell tryptase (K(i)=50.4 microM). The resulting material was treated as "unknown." Our kinetic equation predicts that such adulterated material should show I(50)=0.40 microM, which was identical to the experimentally observed value. The best-fit value of the apparent inhibition constants for the tight-binding inhibitor was K(i)=(0.107+/-0.035)nM, close to the true value of 0.065 nM.

Binding, Competitive↗

Dietary supplement Standard Reference Materials.

A new category of Standard Reference Materials (SRMs) based on dietary supplements is under development by the National Institute of Standards and Technology (NIST), with certified values for organic constituents and selected trace elements. These materials are provided primarily for use in method development and as control materials. The SRMs will assist manufacturers of dietary supplements in characterizing raw materials for potency, authenticity, and contamination or adulteration. In addition, the SRMs will assist in assessment of consistency and quality in finished products. The goal of this ongoing effort is to provide tools to the dietary supplement industry and measurement communities that will lead to improved quality of dietary supplements, and ultimately reduce public health risks that could potentially be associated with these products.

Dietary Supplements↗

Analysis of coptisine, berberine and palmatine in adulterated Chinese medicine by capillary electrophoresis-electrospray ion trap mass spectrometry.

Chinese medicine preparations contaminated with coptisine, berberine and palmatine were studied by capillary electrophoresis-electrospray ion trap mass spectrometry. The dubious adulterants were identified by their retention times, molecular ions and specific fragment ions produced from collision induced dissociation. The results showed that, in comparison with CE-UV and capillary electrophoresis-electrospray mass spectrometry (CE-ESI-MS), more reliable identification could be achieved with CE-ESI-MS-MS using ion trap mass spectrometry.

Berberine↗

Carbohydrate specification limits for the authenticity assessment of soluble (instant) coffee: statistical approach.

Carbohydrates are very good tracers for the authenticity assessment of soluble (instant) coffee. Total glucose and total xylose were determined in 1002 samples of commercial soluble coffees using high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) according to AOAC Method 995.13 and ISO standard 11292. The samples analyzed included both authentic and adulterated coffees but were all sold as 100% pure soluble coffee. The statistical model, called "mixture of distributions," was applied to all results and allowed to derive the maximum content of the 2 carbohydrates in the population of products corresponding to pure soluble coffee: 2.32% for total glucose and 0.42% for total xylose. The specification limits, above which a soluble coffee should be considered as adulterated, were calculated by adding the corresponding expanded measurement uncertainty to the maximum content. Specification limits of 2.46% for total glucose and 0.45% for total xylose were obtained. The data statistically confirm previously established criteria for the authenticity assessment of commercial soluble coffee.

Anions↗

Contaminated street heroin. Relationship to clinical infections.

Thirty-one samples of street heroin were analyzed bacteriologically and chemically as to their microbial burden and chemical adulterants (fillers). Sixty-one percent of the samples were positive for microbial growth. Many species were isolated from the positive samples with Bacillus sp (79%) and Aspergillus sp (10%) predominating. The level of contamination ranged from 1.6 X 10(2) to 3.7 X 10(4) organisms per gram. We obtained cultures from 16 addicts from the Chicago area and 21 from the New Orleans area who had soft-tissue infections related to their habit. Infections in this group of patients were usually polymicrobial; however, there was no correlation between the organisms recovered from street heroin and the addicts' infections. Most drug-related infections appear to be related to the addicts' own oral and dermal microflora. No correlation was observed between the chemical fillers and the bacteria recovered from the heroin.

Bacterial Infections↗

Cocaine and lidocaine in combination are synergistic convulsants.

The abuse of cocaine has dramatically increased in the recent decade. Cocaine obtained on the illegal market is rarely found in pure form. Most often it is adulterated with various substances, especially other local anesthetics. Lidocaine is one of the most common local anesthetics employed for adulteration of illicit cocaine. Toxicity due to the simultaneous ingestion of cocaine and lidocaine has been reported. Acute toxicity to cocaine and other local anesthetics is manifested in central nervous system aberrations, such as seizures and convulsions. This study investigated the convulsant potency of cocaine and lidocaine alone and in combination. Rats were administered intravenous injections of 5 mg/kg or 20 mg/kg of cocaine or lidocaine alone and in combination in equal proportion. Seizure activity and intensity were evaluated. The plasma concentration and brain content of each agent was also determined at the time of toxicity. The administration of 5 mg/kg of each drug alone did not yield seizure activity. However, the concomitant administration of 5 mg/kg of both cocaine and lidocaine produced a seizure response nearly equal to that produced after administration of 20 mg/kg of cocaine alone. Diazepam pre-treatment successfully antagonized the seizures induced by cocaine and lidocaine and raised the seizure threshold dose for the combination treatment by approximately four fold. The results suggest that cocaine and lidocaine interact synergistically to increase seizure activity and that the nature of this response occurs in part through a depression of inhibitory neuronal transmission.

Animals↗

[A pharmacognostical study on herba Spirodelae and its adulterants].

OBJECTIVE: To Study the characteristics of Herba Spirodelae(Spirodela polyrrhiza) and its adulterants S. oligorrhiza and Lemna minor for identification. METHOD: The characteristics were compared and identified morphologically and histologically. RESULT: The morphological and histological characteristics of S. polyrrhiza, S. oligorrhiza and L. minor are different from each other. Several tables, keys and drawings are given. CONCLUSION: The main macroscopical and microscopical characteristics can be used fo differentiate S. polyrrhiza from its adultrants.

Drug Contamination↗

The quantitative analysis of heroin, methadone and their metabolites and the simultaneous detection of cocaine, acetylcodeine and their metabolites in human plasma by high-performance liquid chromatography coupled with tandem mass spectrometry.

For a pharmacokinetic-pharmacodynamic study in opioid tolerant patients, who were treated with heroin in combination with methadone, a liquid chromatographic assay with tandem mass spectrometry detection (LC-MS/MS) was developed for the simultaneous determination of heroin, methadone, heroin metabolites 6-monoacetylmorphine, morphine, and morphine-6 and 3-glucuronide and methadone metabolite EMDP. To detect any abuse of substances besides the prescribed opioids the assay was extended with the detection of cocaine, its metabolites benzoylecgonine and norcocaine and illicit heroin adulterants acetylcodeine and codeine. Heroin-d6, morphine-d3, morphine-3-glucuronide-d3 and methadone-d9 were used as internal standards. The sample pre-treatment consisted of solid phase extraction using mixed mode sorbent columns (MCX Oasis). Chromatographic separation was performed at 25 degrees C on a reversed phase Zorbax column with a gradient mobile phase consisting of ammonium formate (pH 4.0) and acetonitrile. The run time was 15 min. MS with relatively mild electrospray ionisation under atmospheric pressure was applied. The triple quadrupole MS was operating in the positive ion mode and multiple reaction monitoring (MRM) was used for drug quantification. The method was validated over a concentration range of 5-500 ng/mL for all analytes. The total recovery of heroin varied between 86 and 96% and of the heroin metabolites between 76 and 101%. Intra-assay and inter-assay accuracy and precision of all analytes were always within the designated limits (< or =20% at lower limit of quantification (LLQ) and < or =15% for other samples). This specific and sensitive assay was successfully applied in pharmacokinetic studies with medically prescribed heroin and toxicological cases.

Administration, Inhalation↗

Alternative therapies and medical science: designing clinical trials of alternative/complementary medicines--is evidence-based traditional Chinese medicine attainable?

Evidence-based traditional Chinese medicine is attainable. With good planning and a positive attitude, the remedies used in traditional Chinese medicine (TCM) and Chinese proprietary medicines can be studied at a standard acceptable to modern science. The identification of an active principal should not delay the search for effective remedies from the TCM pharmacopoeia. Herbal mixtures can be validly tested to establish their efficacy. Problems with potential batch-to-batch variation can be circumvented by appropriate randomization. Subsequent independent screening and randomization to treatment and placebo arms can allow for the individualization of treatments by TCM practitioners. However, clearly defined treatments are required and should be recorded in a manner that enables other suitably trained researchers to reproduce them reliably (e.g., using prescriptions in Chinese). Quality control of TCM is a prerequisite of credible clinical trials. Correct natural ingredients must be used without adulteration or erroneous substitution. Evidence of safety in man is essential, and in lieu of data from formal toxicity studies, clear, convincing, and impartial evidence of safety is needed based on their long-term use in mainstream TCM practice backed up by publications in the Chinese medical/scientific literature.

Clinical Medicine↗

Antibiotic and sulfonamide agents in bob veal calf muscle, liver, and kidney.

During the fiscal year 1988, USDA-FSIS detected 3,095 antimicrobial violations in bob veal calves, using the calf antibiotic and sulfonamide test. Of the 3,095 carcass submissions involved, 945 were tested further to identify the causative agents. The results of tests on the available kidney, liver, and muscle specimens are reported. Kidney specimens yielded a specific agent most often (71.2%), with neomycin (42.6%) being cited most among agents found in kidneys. Neomycin was found less frequently in liver (4.5%) and muscle (0.2%). Among all tissues, unidentified microbial inhibitors were either the largest or second largest category found (kidney, 10.5%; liver, 27.1%; muscle, 7.8%), and no other agent exceeded 7.0% (streptomycin in kidney). The proportion of liver and muscle specimens that had unidentified microbial inhibitors is particularly important because the next most common classes were streptomycin in liver at 5.5% and sulfamethazine in muscle at 2%. The frequency of unidentified microbial inhibitors may justify the addition of tests to the FSIS battery for identification of agents. Not all tissues were tested for sulfonamides, hence these agents are likely to have been underreported. Less than 10% of the muscle specimens evaluated yielded an agent, suggesting most calf antibiotic and sulfonamide test-positive carcasses may have been safe with regard to residues in meat, although organs might have been adulterated. Specimens for verification were not selected completely randomly from the population of all calf antibiotic and sulfonamide test-positive animals and calves selected for testing were not chosen strictly by random sampling; therefore, extrapolation of the contents of this report to the bob veal calf industry must be done with caution.

Animals↗

Enzyme immunoassay for screening of sulfathiazole in honey.

A simple enzyme immunoassay (EIA) was developed to screen honey samples for sulfathiazole (ST) adulteration. Honey samples required only a 30-fold dilution before use in the procedure. Because 96 well microtiter plates were used and only 100 microL of diluted honey sample was required per well, numerous replicates or samples could be tested simultaneously. The EIA was able to detect at least 0.3 ppm levels of ST in honey and also provide a rough quantitation of ST amounts.

Drug Residues↗