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Regulatory and ethical issues with dietary supplements.

Dietary supplements are commonly used, and many are effective or hold promise for treating various conditions. However, they do not require Food and Drug Administration (FDA) approval. Impurities and adulterants have been found in the products, mostly due to the lack of requirements for good manufacturing practices. In addition, as no standardization is required, the active ingredient may be absent or highly variable among manufacturers. The FDA published its 10-year plan for dietary supplements that addresses safety, labeling, boundaries, enforcement, research, and outreach. This endeavor, if put into place, will be instrumental in providing consumers with more confidence in the safety, composition, and labeling of dietary supplements.

Advertising↗

Side-effects of complementary and alternative medicine.

Complementary and alternative medicine are increasingly used to diagnose or treat allergic diseases, and numerous studies have reported benefits of this type of medicine. This article presents a review of the literature on risks of these methods. The potential sensitizing capacity of numerous herbal remedies may lead to allergic contact dermatitis and more rarely to IgE-mediated clinical symptoms. Mechanical injuries may be observed following acupuncture leading to pneumothorax, cardiac tamponade or spinal injury. Infectious complications after acupuncture include hepatitis and bacterial endocariditis. Organ toxicity has been observed associated with various herbal preparations involving the liver, kidneys, and the heart. Some herbs may have cancerogenic properties. Severe nutritional deficiencies can occur in infants and small children given strict alternative diets, resembling 'kwashiorkor'. Finally, among other miscellaneous adverse effects, adulteration with steroids, and herbal and drug interactions are discussed. The pattern of side-effects is similar to that observed by the use of conventional medicine. Therefore, caution may be justified using both conventional and unconventional methods. Only if the benefit is proven and the side-effects are established, should a given method be chosen.

Acupuncture Therapy↗

Molecular authentication of the animal crude drug Sailonggu (bone of Myospalax baileyi).

Two pairs of allele-specific diagnostic primers (SL1L/SL1H and SL2L/SL2H) for distinguishing the Chinese crude drug Sailonggu (bone of plateau zokor, Myospalax baileyi) from its substitutes were designed based on complete sequences of mitochondrial 12S rRNA and cytochrome b genes of the original animals of Myospalacinae, bamboo rat Rhizomys sinensis and black lipped pika Ochotona curzoniae. Total DNA was extracted from crude drug samples and original animals. Allele-specific diagnostic PCRs were performed using these primers with the total DNA as a template annealing at 65 degrees C. Positive amplifications were obtained from all DNA templates of Sailonggu and M. baileyi, whereas negative amplifications resulted from those of other zokors, the bamboo rat and black lipped pika. These results indicate that Sailonggu samples can be definitely distinguished from their substitutes by diagnostic PCR, and no incorrect discrimination was found under the same reaction conditions. Each of the two diagnostic primer pairs can be used to distinguish crude drug Sailonggu from its substitutes or adulterants. The three Sailonggu samples studied were diagnosed as genuine Sailonggu. In addition, the results of sequence alignment and phylogenetic analysis are congruent with that of the allele-specific diagnostic PCR.

Alleles↗

[Herbal preparation-induced liver injury].

Recently the use of herbal preparations as remedies for various medical conditions, has been rapidly increasing in Korea. In our previous study, 38.9% of patients with chronic liver disease were found to use some sorts of herbal preparations. They believe herbal preparations are safe although the ingredients has never been rigorously substantiated. Toxicities of certain herbal preparations are caused by their contaminants and adulterated ingredients or concurrently used conventional drugs rather than specific components of the herbal preparations. Furthermore, in most instances, multiple herbal ingredients are used by the prescribers of oriental medicine. All of these conditions frequently impose diagnostic difficulties. There are myriads of plant-derived hepatotoxic substances which may or may not cause liver injury in individuals. The severity of liver injury depends largely on the toxicity of the substance, the amount of exposure and the individual's susceptibility. These toxic substances cause liver injury not only through the mechanism of intrinsic hepatotoxicity but also through the idiosyncrasy as in conventional drug-induced injury. Therefore, theoretically, it is possible to apply pre-existing CAMs (Causality Assessment Methods) to the assessment of causality in cases with diagnostic difficulties.

Chemical and Drug Induced Liver Injury↗

An assay evaluation of the methylene blue method for the detection of anionic surfactants in urine.

Adding detergent to urine intended for drug testing is one of many ways to adulterate the specimen. This modified methylene blue procedure allows the detection and quantitation of anionic surfactants in urine. One-hundred urine specimens that exhibited normal foaming when shaken gave anionic surfactant values lower than 36 microg/mL with a mean of 8.73 microg/mL. Most of the suspected adulterated specimens and spiked samples with only 100 microL of detergent in 60 mL of urine had values greater than 750 microg/mL. Based on the analysis of negative samples, a urine specimen with an anionic surfactant level of 100 microg/mL or greater could be considered adulterated and most likely will have levels greater than 800 microg/mL.

Drug Contamination↗

Testing for anabolic steroids in hair: a review.

It is generally accepted that chemical testing of biological fluids is the most objective means of diagnosis of drug use. The presence of a drug analyte in a biological specimen can be used to document exposure. The standard in drug testing is the immunoassay screen, followed by the gas chromatographic-mass spectrometric confirmation conducted on a urine sample. In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional biological specimens such as hair. The advantages of this sample over traditional media like urine and blood are obvious: collection is almost noninvasive, relatively easy to perform, and in forensic situations it may be achieved under close supervision of law enforcement officers to prevent adulteration or substitution. Moreover, the window of drug detection is dramatically extended to weeks, months or even years. The aim of this review is to document the current detection of anabolic steroids in hair.

Anabolic Agents↗

Neuroleptic-induced deficits in food and water regulation: similarities to the lateral hypothalamic syndrome.

The role of central dopaminergic mechanisms in the regulation of food and water intake was assessed by examining the effects of haloperidol and pimozide on various measures of feeding and drinking in rats. Haloperidol (0.20 mg/kg) or pimozide (0.45 mg/kg) did not significantly affect 1-hr water intake in response to 24 hrs of water deprivation, nor did they influence 2-hr food intake after 24 hrs food deprivation. However both pimozide and haloperidol significantly reduced drinking in response to injections of hypertonic saline. In addition, animals pretreated with these drugs drank less than controls in the absence of food (a measure of "non-prandial" drinking), and drank less than controls when the water was adulterated with quinine (a measure of "finickiness"). These drugs also significantly reduced food intake in response to injections of insulin and attenuated amphetamine anorexia. These deficits are similar to those observed after electrolytic lesions of the lateral hypothalamus or after 6-hydroxydopamine lesions of the substantia nigra. Because haloperidol and pimozide block central dopaminergic receptor sites, the present findings are consistent with the hypothesis that part of the lateral hypothalamic syndrome is the result of damage to the dopaminergic nigro-neostriatal projection. Finally, the data suggest that the changes in feeding and drinking induced by haloperidol and pimozide reflect genuine homeostatic deficits rather than being due to a neuroleptic-induced motor dysfunction.

Animals↗

Value of hair analysis in postmortem toxicology.

It is generally accepted that chemical testing of biological fluids is the most objective means of diagnosis of drug use. The presence of a drug analyte in a biological specimen can be used to document exposure. The standard in postmortem drug testing is a general unknown screening, followed by the gas chromatographic/mass spectrometric confirmation conducted on a whole blood sample. In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional biological specimens such as hair. The advantages of this sample over traditional media, like urine and blood, are obvious: collection is almost non-invasive, relatively easy to perform, and in forensic situations it may be achieved under close supervision of law enforcement officers to prevent adulteration or substitution. Moreover, the window of drug detection is dramatically extended to weeks, months or even years. The aim of this review is to document the current status of hair analysis in postmortem toxicology.

Forensic Medicine↗

[Sequencing of Cyt b gene fragments and PCR identification of "jinqian baihuashe" (Bungarus parvus) and its adulterants].

DNAs extracted from both "Jinqian Baihuashe" (Bungarus parvus) and its adulterants and original animals of the crude snake drugs were used as templates for Cyt b gene fragment amplification. The sequence data of the fragments showed that the differences of the sequence between Bungarus parvus and its adulterants were far greater than that between intraspecific variations of Bungarus parvus. Therefore, the Cyt b gene fragment was a good molecular genetic marker for the authentication of Bungarus parvus. On the basis of the sequence data, a pair of specialized primers, BuL-1 and BuH-1 was designed for the PCR identification of Bungarus parvus. The effectiveness of the primers were examined at a series of anneal temperatures. The results showed that Bungarus parvus samples could be absolutely distinguished when the anneal temperatures were 60 degrees C-65 degrees C, whereas no incorrect or missing discrimination was found at these temperatures. The results also showed that the powder of Bungarus parvus which was mixed with powders of three other crude snake drugs may be detected by the PCR identification. This indicates that PCR identification may be a new method for examining the compositions of Chinese patent medicine.

Animals↗

Applications of liquid chromatography-tandem mass spectrometry in drug and biomedical analyses.

BACKGROUND: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is one of the major tools for bioanalytical works. These instruments can be used for quantitative determination of plasma samples in pharmacokinetic studies. LC-MS/MS techniques frequently provide specific, selective and sensitive quantitative results often with reduced sample preparation and analysis time relative to other commonly employed techniques. METHODS: The applications of these instruments include analysis of nine corticosteroids illegally adulterated in traditional Chinese medicines, identification of drug metabolites of roxithromycin, propafenone and some glucuronide conjugates and the quantitative determination of plasma samples containing amlodipine, nitrendipine, flupirtine and their major metabolites. CONCLUSIONS: LCQ is ideally suited for the rapid identification of metabolites because it provides on-line LC/MS(n) capability, enabling multiple MS stages to obtain the maximum amount of structural information, while TSQ provides excellent precise and accurate results for quantitative assays at very low detection limits.

Amlodipine↗

Investigation of nitrite adulteration on the immunoassay and GC-MS analysis of cannabinoids in urine specimens.

Nitrite ion has been identified as the active ingredient of two commercial adulterants that could cause discrepant results between the immunoassay screening and gas chromatographic-mass spectrometric (GC-MS) confirmation of 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in urine. Procedures to chemically convert the nitrite ion at the beginning of sample preparation for GC-MS analysis may not overcome all nitrite adulteration cases because portions of the THCCOOH might have been lost between the time of sample collection and the time of analysis. This study was conducted to further investigate the influence of both urine sample matrix and the duration of nitrite exposure on nitrite interference of THCCOOH detection. Forty clinical "THC-positive samples" that had been screened and confirmed positive for the presence of THCCOOH were spiked with 0.15M or 0.3M of nitrite. The levels of THCCOOH at various time intervals after nitrite spiking were monitored by instrument-based cannabinoids immunoassays (Syva EMIT d.a.u. and/or Roche Abuscreen ONLINE assays) and by an onsite THC immunoassay (Roche ONTRAK TESTSTIK). Results from this report demonstrate that the two outstanding "urine specimen factors" that dictated the effectiveness of the nitrite adulteration were urinary pH and the original drug concentration before nitrite spiking. Significant decreases in the immunoassay results could be observed within 4 h of nitrite treatment in the majority of samples with acidic urinary pH values. Regardless of their original concentration of THCCOOH (GC-MS ranging from 33 to 488 ng/mL), all of the 20 samples that had acidic pH values gave negative immunoassay results 1 day after nitrite adulteration. In contrast, the immunoassay results of samples with neutral or basic pH values were less affected by nitrite exposure in the same studies. Approximately two-thirds of the samples with pH values greater than 7.0 remained immunoassay-positive 3 days after nitrite spiking. Nevertheless, some of the adulterated urine that showed no change in immunoassay results might exhibit significant decrease in GC-MS recoveries even with bisulfite treatment, collaborating with the observations that a portion of samples screened positive with THC immunoassay in the laboratory could fail to confirm with GC-MS analysis. The decrease or loss of immunoassay detectable cannabinoid cross-reactives in acidic "THC-positive samples" can be attenuated by chemically increasing the pH value of the samples to the basic pH range.

Dronabinol↗

Comparison of point-of-collection screening of drugs of abuse in oral fluid with a laboratory-based urine screen.

Oral fluid is becoming increasingly useful for the detection of drugs, since it is a non-invasive specimen to collect and, because collection is directly observed, it is difficult to adulterate. A point-of-collection (POCT) oral fluid drug analysis kit has been developed for use in many drug testing situations. This paper summarizes the results of field evaluations of the ORALscreen System for screening of drugs in oral fluid. The ORALscreen System consists of an oral fluid collection device and a test device containing a lateral flow membrane immunoassay system. Paired samples (oral fluid and urine) were collected from drug users and the results from the ORALscreen POCT system were compared to urine screening results conducted in a licensed laboratory. The results demonstrate that the ORALscreen System has excellent percent agreement with the laboratory-based urine screening test results for the detection of cocaine and opiates through 2.5-3 days following drug use, respectively. Tetrahydrocannabinol (THC) was detected by ORALscreen on the day of use and 1 day after use. Good correlation between urine and oral fluid screening results was observed for the methamphetamine positive samples; however, the number of days following drug use was not determined.

Clinical Laboratory Techniques↗

A descriptive study of an epidemic of poisoning caused by heroin adulterated with scopolamine.

OBJECTIVE: Adulterants, contaminants, and diluents are all examples of additives to street drugs. Some of these additives may be pharmacologically active; however, it is unusual for them to cause toxic side effects. In the spring of 1995, a new form of heroin appeared in New York City, spreading to other East Coast cities, that was adulterated with scopolamine. It caused severe anticholinergic toxicity in heroin users with patients often presenting to emergency departments in great numbers. This is a report of the demographics and clinical characteristics of the epidemic. METHODS: A combination of prospective and retrospective data collection from the New York City, New Jersey, Delaware Valley, and Maryland Poison Centers. The primary measurements were age, sex, route of drug use, vital signs, signs and symptoms, disposition, and treatment. RESULTS: Of the 370 cases reported to the participating poison centers, 129 were excluded from the final analysis because of insufficient data. Of the patients who used this product, 55% presented with signs and symptoms of heroin toxicity but then became severely agitated with anticholinergic symptoms when naloxone was used to reverse respiratory depression. Nasal insufflation was the route of administration in 34% of the cases. Seizures were rare (3%). Ninety percent required admission, and half were admitted to a critical care unit. CONCLUSIONS: Adulteration of street drugs can lead to toxic epidemics. Poison centers are essential for identification of these trends and are the primary source of information on diagnosis and treatment.

Adolescent↗

The detection and estimation of (A) arsenic in opium, and (B) strychnine in opium and heroin, as a means of identification of their respective sources.

Samples of opium with arsenic as an adulterant, and both opium and heroin with strychnine as an adulterant are not infrequently encountered in the local drug scene. The paper describes a method for the possible identification of the sources of opium and heroin in the local market on the basis of an accurate quantitation of the adulterant arsenic and strychnine contents of the respective samples. A possible extension of this concept, would be the possibility of a similar identification of sources outside the country with a view to establishing channels of entry from abroad. Arsenic is determined by the Gutzeit method while strychnine is estimated by high performance liquid chromatography (HPLC).

Arsenic↗

Hair analysis for drugs of abuse. Plausibility of interpretation.

Over more than 20 years hair analysis for drugs has been gaining increasing attention and recognition in various toxicological fields as preemployment and employment screening, forensic sciences, doping control of banned substances, clinical diagnostics in health problems. Hair analysis for drugs can expand the toxicological examination of conventional materials and thus contribute with additional important information to the complex evaluation of a certain case. Hair is a unique material for the retrospective investigation of chronic drug consumption, intentional or unintentional chronic poisoning in criminal cases, gestational drug exposure or environmental exposure to pollutants and adulterants and with specific ultrasensitive procedures allow to demonstrate even a previous single dose administration in a very low amount. Assuming the ideal hair steady and uniform growth, segmental hair analysis can provide the information about the time course of the substance use or exposure. However, the physiological background of hair growth, mechanisms of drug incorporation are not simple, not yet understood in full details and need not be evaluated exactly in all cases. The hair sampling, storage, sample preparation, analytical performance themselves are also very important for final results. Different laboratory attitudes can produce different results. The full information on circumstances of the case examined must be taken into account during interpretation. The pitfalls in hair analysis should be known and avoided to assure the responsible and correct interpretation of laboratory results adequate to an individual case.

Forensic Toxicology↗