It is claimed that ayurvedic/herbal healthcare products (AHPs) are safe because of their natural origin. However, several reports exist of adulteration of AHPs with synthetic drugs. In this study, a generalized strategy was developed using LC-MS/TOF for the detection and verification of steroidal and anti-inflammatory drugs in 58 AHPs collected from various parts of India. The strategy involved recording of mass spectral information for standard drugs-including ionization mode (ESI/APCI - ve or + ve), mass spectrum, accurate mass, identification of qualifier fragments (two), extracted ion chromatograms (EICs), isotopic pattern and determination of UV max (nm)-through UV-PDA studies. Adulteration was then detected in AHPs primarily through comparison of EICs at accurate m/z for molecular ion peaks and R(T) matching with the standard. It was confirmed by spiking with the standards, and matching mass spectrum, accurate mass, R(T) of qualifier fragments, isotopic pattern and UV spectrum of the standards with the adulterant peaks in AHPs. Dexamethasone and diclofenac were detected as adulterants in ten AHPs whereas one AHP tested positive for piroxicam and another for dexamethasone. All the adulterated products were sold by the healthcare practitioners, while no product marketed by manufacturers or chemist shops had this problem. The study showed that LC-MS/TOF-based screening could be used as a rapid approach to monitor adulteration of steroids and anti-inflammatory drugs in AHPs. Copyright (c) 2009 John Wiley & Sons, Ltd.

Two microscale separation techniques for the analysis of bioactive naphthoquinones in Eleutherine americana were developed and validated. By MEKC four compounds (eleuthoside B, isoeleutherin, eleutherol and eleutherinoside A) could be determined in plant extracts using an aqueous electrolyte solution composed of 25 mM sodium tetraborate, 50 mM sodium cholate and 20% THF. CEC on a polymeric methacrylate-based monolith with strong cationic properties showed promising results, as it additionally enabled the separation of two enantiomers, eleutherin and isoeleutherin. The mobile phase for CEC experiments comprised 3 mM ammonium formate in a mixture of ACN and water. At an applied voltage of -25 kV, all five markers were baseline separated in less than 12 min. Both methods were successfully validated for linearity (MEKC: R(2)>/=0.999; CEC: R(2)>/=0.997), sensitivity (MEKC: LOD=4-5 mug/mL; CEC: LOD=2-8 mug/mL), accuracy (MEKC: 96.5-102.7% recovery; CEC: 97.1-103.5% recovery) and precision (MEKC: sigma(rel)</=2.43%; CEC: sigma(rel)</=2.21%). The quantitative analysis of naphthoquinone derivatives in several E. americana samples showed that both methods are suitable for practical applications, because the results were well comparable to those obtained by established techniques such as HPLC.

The safety of dietary supplements is questionable as there have been occasional reports of products contaminated with illegal adulterants. The present study was carried out to develop trustworthy methodologies to screen for six anti-diabetic drugs (phenformin, rosiglitazone, glipizide, glimepiride, glybenclamide and gliclazide) and six anti-obesity drugs (ephedrine, fenfluramine, T3, T4, fluoxetine and sibutramine) in dietary supplements. A simultaneous determination method of the 12 drugs by liquid chromatography coupled with a photodiode array (LC/PDA) was established and was validated for linearity (r(2)> 0.99), precision (RSD <13.3%), recoveries (88.8-115.9%) and reproducibility. Sibutramine and its analogs, N-desmethylsibutramine, were subject to further investigation by LC/MS/MS because they were one of the major illegal adulterants. Our proposed method to monitor illegal drug adulterations in dietary supplements using LC/PDA is a simple and reliable, and therefore applicable to routine drug-adulteration screening. Copyright (c) 2009 John Wiley & Sons, Ltd.

A high-performance liquid chromatographic method, coupled with UV detection and electrospray ionization mass spectrometry (HPLC-UV-ESI-MS), is developed for the simultaneous determination of the illegal additives sibutramine and its metabolite N-di-desmethylsibutramine in dietary supplements for weight control. The separation is achieved on a Spherisorb C8 reversed-phase column, employing acetonitrile and an aqueous 0.2% formic acid solution containing 20mM ammonium acetate as mobile phases in a gradient mode. UV detection is used for quantitation at a wavelength of 223 nm. Identification of target compounds is completed by ESI-MS using selected ion recording at m/z 280 for sibutramine and m/z 252 for N-di-desmethylsibutramine. Calibration curves are linear over the range of 0.025-1.0 mg/mL for sibutramine and N-di-desmethylsibutramine. Correlation coefficients are better than 0.9990. The intra- and inter-day precision and accuracy for sibutramine and N-di-desmethylsibutramine are acceptable. The method is successfully applied to the analysis of natural dietary supplement samples.

A liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method was developed for the simultaneous determination of six synthetic adulterants, namely fenfluramine, phenolphthalein, N-di-desmethyl sibutramine, N-mono-desmethyl sibutramine, sibutramine, and orlistat. The method was applied to the analysis of herbal weight-reducing dietary supplements. Chromatographic separation of the analytes on a C(8) reversed-phase column was achieved using a gradient elution of solvent A: acetonitrile and solvent B: aqueous 20 mM ammonium formate solution. Sildenafil was utilized as an internal standard for quantification. The MS detector was operated in positive electrospray ionization mode. Selected-ion monitoring (SIM) was carried out for m/z 232, 319, 252, 266, 280, 496, and 475 for fenfluramine, phenolphthalein, N-di-desmethyl sibutramine, N-mono-desmethyl sibutramine, sibutramine, orlistat, and sildenafil, respectively. The method was validated for accuracy, precision, linearity, and selectivity. The limits of detection for the six synthetic adulterants ranged from 0.0018 to 0.73 microg g(-1). The proposed method was used for a small survey of 22 dietary supplements of which eleven samples were adulterated with phenolphthalein, N-mono-desmethyl sibutramine, and sibutramine at levels from 0.212 to 96.2 mg g(-1).

Since 1999 several groups have analyzed nutritional supplements with mass spectrometric methods (GC/MS, LC/MS/MS) for contaminations and adulterations with doping substances.These investigations showed that nutritional supplements contained prohibited stimulants as ephedrines, caffeine, methylenedioxymetamphetamie and sibutramine, which were not declared on the labels. An international study performed in 2001 and 2002 on 634 nutritional supplements that were purchased in 13 different countries showed that about 15% of the nonhormonal nutritional supplements were contaminated with anabolic-androgenic steroids (mainly prohormones). Since 2002, also products intentionally faked with high amounts of 'classic' anabolic steroids such as metandienone, stanozolol, boldenone, dehydrochloromethyl-testosterone, oxandrolone etc. have been detected on the nutritional supplement market. These anabolic steroids were not declared on the labels either. The sources of these anabolic steroids are probably Chinese pharmaceutical companies, which sell bulk material of anabolic steroids. In 2005 vitamin C, multivitamin and magnesium tablets were confiscated, which contained cross-contaminations of stanozolol and metandienone. Since 2002 new 'designer' steroids such as prostanozol, methasterone, androstatrienedione etc. have been offered on the nutritional supplement market. In the near future also cross-contaminations with these steroids are expected. Recently a nutritional supplement for weight loss was found to contain the beta2-agonist clenbuterol. The application of such nutritional supplements is connected with a high risk of inadvertent doping cases and a health risk. For the detection of new 'designer' steroids in nutritional supplements, mass spectrometric strategies (GC/MS, LC/MS/MS) are presented. Copyright (c) 2008 John Wiley & Sons, Ltd.

In several studies it has been demonstrated that products containing pharmaceutically active ingredients are marketed as dietary supplements. Most of these products contain anabolic steroids. Recently products for weight loss containing active drugs have also appeared on the market. In the present case a healthy male ordered the product 'Anabolic burner' via the Internet. The product was received from a German dispatcher and paid by bank transfer to a German bank account. After ingesting one tablet he reported tremor and delivered a urine sample. This urine was found to contain 2 ng/mL of clenbuterol utilizing LC-MS/MS analysis. Additionally the product itself was analyzed with GC-MS for clenbuterol, yielding a content of about 30 microg per tablet. The beta-2 agonist clenbuterol is only legally available on prescription and is classified as prohibited doping substance in sports. The present case for the first time confirms the presence of clenbuterol in a dietary supplement. It again demonstrates the common problem with products on the supplement market, where non-licensed pharmaceuticals and doping substances are easily available. The ingestion of these products containing additions of therapeutic drugs can lead to side effects and/or interactions with conventional medicines. Copyright (c) 2007 John Wiley & Sons, Ltd.

In Cannabis sativa, Delta9-Tetrahydrocannabinolic acid-A (Delta9-THCA-A) is the non-psychoactive precursor of Delta9-tetrahydrocannabinol (Delta9-THC). In fresh plant material, about 90% of the total Delta9-THC is available as Delta9-THCA-A. When heated (smoked or baked), Delta9-THCA-A is only partially converted to Delta9-THC and therefore, Delta9-THCA-A can be detected in serum and urine of cannabis consumers. The aim of the presented study was to identify the metabolites of Delta9-THCA-A and to examine particularly whether oral intake of Delta9-THCA-A leads to in vivo formation of Delta9-THC in a rat model. After oral application of pure Delta9-THCA-A to rats (15 mg/kg body mass), urine samples were collected and metabolites were isolated and identified by liquid chromatography-mass spectrometry (LC-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high resolution LC-MS using time of flight-mass spectrometry (TOF-MS) for accurate mass measurement. For detection of Delta9-THC and its metabolites, urine extracts were analyzed by gas chromatography-mass spectrometry (GC-MS). The identified metabolites show that Delta9-THCA-A undergoes a hydroxylation in position 11 to 11-hydroxy-Delta9-tetrahydrocannabinolic acid-A (11-OH-Delta9-THCA-A), which is further oxidized via the intermediate aldehyde 11-oxo-Delta9-THCA-A to 11-nor-9-carboxy-Delta9-tetrahydrocannabinolic acid-A (Delta9-THCA-A-COOH). Glucuronides of the parent compound and both main metabolites were identified in the rat urine as well. Furthermore, Delta9-THCA-A undergoes hydroxylation in position 8 to 8-alpha- and 8-beta-hydroxy-Delta9-tetrahydrocannabinolic acid-A, respectively,(8alpha-Hydroxy-Delta9-THCA-A and 8beta-Hydroxy-Delta9-THCA-A, respectively) followed by dehydration. Both monohydroxylated metabolites were further oxidized to their bishydroxylated forms. Several glucuronidation conjugates of these metabolites were identified. In vivo conversion of Delta9-THCA-A to Delta9-THC was not observed. Copyright (c) 2009 John Wiley & Sons, Ltd.

BACKGROUND: In recent years, the market for dietary supplements has grown. International products are readily available for purchase over the Internet. We report 17 cases of poisoning with a single product, said to be of purely herbal origin, that was bought over the Internet. A complete declaration of the ingredients was not available. METHODS: We performed a retrospective study of cases of poisoning documented by the Göttingen and Freiburg poison information centers from 2005 to 2008. In 4 cases, we were able to perform toxicological analyses of leftover capsules and urine samples. RESULTS: The manifestations of poisoning in the 17 documented cases included malaise, tachycardia, headache, agitation, arterial hypertension, nausea, vomiting, dyspnea, insomnia, left-sided chest pressure, elevated temperature, and, in two cases, psychosis after the substance was combined with atomoxetine and methylphenidate and with citalopram, olanzapine, and chlorprothixene. The frequency of cases rose markedly in the last year of the study. The toxicological analyses of all samples studied revealed sibutramine. The dose in each capsule was nearly twice the maximum daily dose sibutramine in the medication containing this substance that is licensed for use in Germany. CONCLUSIONS: Products available without a prescription whose contents are claimed to be purely herbal may nonetheless contain synthetic substances in concentrations far above the therapeutic range and may be a cause of poisoning. When taking the history of a patient possibly suffering from an intoxication, the physician should ask specifically about drugs, dietary supplements, and so-called lifestyle products that were obtained without a prescription. It would be desirable for the contents of all such products to be declared, as required by law, so that their suitability for the market can be checked.

This work presents two cases of codeine intoxication in 3-year-old monozygotic twin brothers while treated with a codeine slow-release formulation. One child had to be admitted to the hospital, whereas the other one died at home after aspiration of gastric content. The concentrations of codeine and major metabolites including morphine and corresponding glucuronide conjugates were measured by liquid chromatography-tandem mass spectrometry in serum, urine, cerebrospinal fluid, and brain tissue, respectively. A genetic polymorphism study was carried out in order to determine the ability of the children to metabolize codeine by O-demethylation. A pharmacokinetic calculation was also performed to estimate the administered dose of codeine in question. High concentrations of all substances were found in samples of both children. The pharmacokinetic estimate suggests an overdose of codeine, and the possible reasons for the high opiate concentrations are discussed. Furthermore, the postmortem distribution-during and after resuscitation-might play a major role in the interpretation of postmortem concentration levels.

In spite of the lack of evidence for its efficacy, and of sporadic reports of severe adverse events, codeine is still widely used as an antitussive agent in children. A 3-year-old boy (twin 1) was found lying in vomit and apnoeic at night; he was resuscitated and immediately transferred to our paediatric intensive care unit (PICU). Two and a half hours later, his twin brother (twin 2) was found dead in his bed at home. Twin 1 required mechanical ventilation for 3 days, but he eventually made a full recovery; autopsy in twin 2 showed massive aspiration of gastric content. History revealed that the monozygotic twins had an upper respiratory tract infection for several days and had both been given codeine at a dose of "10 drops per day" by their mother. The blood of both twins was found to contain high levels of codeine and its metabolites. The weight of "10 drops" was determined experimentally and was found to range from 494 to 940 mg. Thus, the highest possible dose given by mother was 23.5 mg of codeine instead of the recommended 10 mg. The twins had identical CYP2D6 gene polymorphisms corresponding to the "extensive metaboliser" type. Conclusions: Because of the variability of drop size drug dosage, dosage "by drops" is unprecise and may result in accidental overdose. The combination of repeated overdosing and extensive metabolism to morphine is likely to have caused apnoea in these twins. These cases illustrate the danger of codeine as an antitussive in young children.

Delta9-Tetrahydrocannabinolic acid A (Delta9-THCA-A) is the precursor of Delta9-tetrahydrocannabinol (Delta9-THC) in hemp plants. During smoking, the non-psychoactive Delta9-THCA-A is converted to Delta9-THC, the main psychoactive component of marihuana and hashish. Although the decarboxylation of Delta9-THCA-A to Delta9-THC was assumed to be complete-which means that no Delta9-THCA-A should be detectable in urine and blood serum of cannabis consumers-we found Delta9-THCA-A in the urine and blood serum samples collected from police controls of drivers suspected for driving under the influence of drugs (DUID). For LC-MS/MS analysis, urine and blood serum samples were prepared by solid-phase extraction. Analysis was performed with a phenylhexyl column using gradient elution with acetonitrile. For detection of Delta9-THCA-A, the mass spectrometer (MS)(SCIEX API 365 triple-quadrupole MS with TurboIonSpray source) was operated in the multiple reaction monitoring (MRM) mode using the following transitions: m/z357 --> 313, m/z357 --> 245 and m/z357 --> 191. Delta9-THCA-A could be detected in the urine and blood serum samples of several cannabis consumers in concentrations of up to 10.8 ng/ml in urine and 14.8 ng/ml in serum. The concentration of Delta9-THCA-A was below the Delta9-THC concentration in most serum samples, resulting in molar ratios of Delta9-THCA-A/Delta9-THC of approximately 5.0-18.6%. Only in one case, where a short elapsed time between the last intake and blood sampling is assumed, the molar ratio was 18.6% in the serum. This indicates differences in elimination kinetics, which need to be investigated in detail. Copyright (c) 2007 John Wiley & Sons, Ltd.

We report the case of attempted suicide with amlodipine, chlorthalidone and mefenamic acid and subsequent medical intensive care measures which resulted in total recovery of a 42-year-old male. After admission to the medical intensive care unit the intoxicated patient was deeply hypotensive and needed fluid replacement, dobutamine and norepinephrine. Additionally insulin and calcium gluconate were given. Since hypotension persisted and the patient developed oliguria, terlipressin was applied and finally showed an effect on blood pressure and on urinary output. A volume overload of 7L in the first 24h resulted in a pulmonary edema. The patient was started on non-invasive ventilation with continuous positive airway pressure (CPAP) and frusemide was added to the therapy with good success. Quantitative determination of amlodipine in plasma samples was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The highest amlodipine concentrations was measured in the plasma sample collected approximately 8h after ingestion of the drug, and was 393mug/L. Four days later, it was possible to stop the treatment with catecholamines, at that time the amlodipine plasma concentration had declined to 132mug/L, still tenfold higher than therapeutic (5-18mug/L). Elimination half-life of amlodipine is approximately 55h. After 6 days in the intensive care unit the patient was transferred to psychiatric treatment. Intensive care management and plasma levels in this intoxication case are compared to data from literature on other cases.

BACKGROUND: To an increasing degree, EtG and EtS are routinely used for the proof of abstinence for purposes of traffic, occupational, addiction and social medicine. This routine use demands further investigations on the sensitivity and specificity of these analytes and the examination of possible genesis of positive EtG and EtS concentrations even without the consumption of ethanol. In vivo fermentation with consecutive formation of EtG and EtS was addressed by experiments with yeast products. METHODS: Two experiments with baker's yeast and brewer's yeast tablets were performed. The ethanol concentrations in urine of the 2 and 4 volunteers, respectively, were detected by HS-GC-FID, EtG and EtS analysis was performed by LC-ESI-MS/MS, and the creatinine concentration was determined using a method based on the Jaffé reaction. RESULTS AND CONCLUSIONS: After the consumption of baker's yeast the maximum concentrations of EtG and EtS normalised to creatinine were found to be 0.67 and 1.41mg/L, respectively, and therefore clearly above the commonly applied cut-off value for the proof of abstinence of 0.1mg/L. In contrast, in this study the, uptake of yeast tablets did not result in a detection of EtG and EtS in urine.

Pesticides are used to protect plants all over the world. Their increasing specificity has been due to utilization of differences in biochemical processes, and has been accompanied by lower human toxicity. Nevertheless cases of poisoning are still observed. While certain toxic substances are provided with characteristic dyes or pigments to facilitate easy identification, no overview of pesticide colors exists. The lack of available product information prompted us to explore the colors and dyes of pesticides registered in Germany, most of which are commercially available worldwide. A compilation of the colors and odors of 207 pesticide products is presented. While some of the substances can be identified by their physical characteristics, in other cases, the range of possibilities can be narrowed by their nature and color.

In abstinence maintenance programs, for reissuing the driving licence and in workplace monitoring programs abstinence from ethanol and its proof are demanded. Various monitoring programs that mainly use ethyl glucuronide (EtG) as alcohol consumption marker have been established. To abstain from ethanol, but not from the taste of alcoholic beverages, in particular non-alcoholic beer has become more and more popular. In Germany, these "alcohol-free" beverages may still have an ethanol content of up to 0.5vol.% without the duty of declaration. Due to severe negative consequences resulting from positive EtG tests, a drinking experiment with 2.5L of non-alcoholic beer per person was performed to address the question of measurable concentrations of the direct metabolites EtG and EtS (ethyl sulphate) in urine and blood. Both alcohol consumption markers - determined by LC-MS/MS - were found in high concentrations: maximum concentrations in urine found in three volunteers were EtG 0.30-0.87mg/L and EtS 0.04-0.07mg/L, i.e., above the often applied cut-off value for the proof of abstinence of 0.1mg EtG/L. In the urine samples of one further volunteer, EtG and EtS concentrations cumulated over-night and reached up to 14.1mg/L EtG and 16.1mg/L EtS in the next morning's urine. Ethanol concentrations in blood and urine samples were negative (determined by HS-GC-FID and by an ADH-based method).

Metabolite identification and metabolite profiling are of major importance in the pharmaceutical and clinical context. However, highly polar and ionic substances are rarely included as analytical tools are missing. In this study, we present a new method for the determination of urinary sulfates, sulfonates, phosphates and other anions of strong acids. The method comprises a CE separation using an acidic BGE (pH</=2) and anodic detection by MS via negative ESI. In this way, only sulfates and sulfonates are detected in the first part of the electropherogram, followed by phosphates and potentially highly acidic carboxylates. The selectivity for sulfur-containing species is proved using extracted ion electropherograms based on certain isotopic ratios. Ethyl sulfate can be determined by this method and, thus, CE-MS can be used for determination of this alcohol consumption marker. An SPE method was developed for the extraction of ethyl sulfate and other organic anions. Several additional compounds can be identified based on the accurate mass determined by the TOF MS in conjunction with databases. However, numerous detected compounds have not been reported in urinary metabolite databases so far. Thus, it is demonstrated that the presented method is complementary to the existing methods for metabolite characterization in urine.

Twenty herbal medicines or dietary supplements marketed as natural slimming products were analysed by diffusion ordered spectroscopy (DOSY)(1)H-nuclear magnetic resonance (NMR) and DOSY-COSY (1)H-NMR. The method allows analysis of the whole sample with the detection of both active and inactive ingredients in these complex matrices. Among the 20 formulations analysed, two were strictly herbal and four had a composition corresponding to declared ingredients on the packaging or the leaflet. The others were all adulterated. Eight formulations contain sibutramine alone at doses ranging from 4.4 to 30.5 mg/capsule. Five formulations contain sibutramine (from 5.0 to 19.6 mg/capsule or tablet) in combination with phenolphthalein (from 4.4 to 66.1 mg/capsule), and the last formulation was adulterated with synephrine (19.5 mg/capsule). Quantification of the actives was carried out with (1)H-NMR. Several other compounds were also characterized including methylsynephrine, vitaberin, sugars, vitamins, etc. DOSY NMR is thus proposed as a useful tool for detection of unexpected adulteration.

Norisoboldine (1,9-dihydroxy-2,10-dimethoxynoraporphine) is one of the major bioactive isoquinoline alkaloids in Linderae Radix, a commonly used Chinese herbal medicine. The aim of this study is to isolate and characterize metabolites of norisoboldine after gavage feeding in rats. High-performance liquid chromatography coupled with electrospray ionization and ion-trap mass spectrometry (HPLC-ESI/MS(n)) was used to identify metabolites of norisoboldine in rat urine and bile samples. A total of five metabolites of norisoboldine were characterized by comparing retention time and UV absorption in HPLC, and by molecular mass and fragmentation pattern of the analytes by mass spectrometry with those of norisoboldine. Two new glucuronide conjugates of norisoboldine, noriosboldine-1-O-beta-d-glucuronide and norisoboldine-9-O-alpha-d-glucuronide, were isolated from rat urine samples and their structures were confirmed by NMR spectroscopy ((1)H,(13)C, HMBC and HSQC) for the first time. The results suggested that glucuronidation and sulfation were involved in metabolic pathways of norisoboldine in rat.

Hepatotoxicity of xenobiotics, which include classical drugs, herbal medicines, and chemical products, represents an important cause of liver diseases. Drug hepatotoxicity exhibits various expressions, practically reproducing all non-iatrogenic liver diseases. Drug hepatitis is the main cause of liver failure, in particular with paracetamol overdosage (near 50 %). Idiosyncratic hepatitis, which are unpredictable, also represent an important cause with a frequency similar to those of viral hepatitis. More than 1200 drugs are recorded as potential hepatotoxics. Causality assessment relies on chronological and clinical criteria and is frequently difficult. Herbal medicines are an increasing cause of liver injury with a large clinical polymorphism as classical drugs. About 50 plants are known to be hepatotoxic. Diagnosis is even more difficult because of frequent auto-medication and purchase via Internet. Chemical products are also responsible of various liver injuries through variable routes of exposition: inhalation of volatile products, ingestion of contaminating product, percutaneous contamination. Their role is particularly difficult to assess because exposure is frequently unknown or intermittent or accidental. Liver reaction may occur a long time after exposure, further increasing difficulties of identification. Several tens of chemicals may be involved. There is no specific treatment for xenobiotic hepatotoxicity, once liver injury as occurred apart paracetamol overdosage. The main measure consists to discontinue this exposition to the responsible compounds to avoid an aggravation of liver injury.

The Chinese herbal medicine 'meizitanc', known as 'LiDa Dai Dai Hua Jiao Nang'(Kunming Dali Industry and Trade, Kunming, Yunnan, China) has been used by many women to support weight loss, even though life-threatening side-effects and deaths have been reported. We report the outcomes of three cases of exposure to 'meizitanc' during early pregnancy. In the first case, the pregnancy continued after the patient stopped taking the drug and at 38 weeks of gestation, the patient delivered a healthy infant. However, in the second and third cases fetal cardiac activities were not detected on obstetric follow-up and both pregnancies were terminated due to missed abortion. To our knowledge, this is the first report of exposure to meizitanc during pregnancy. Although herbal medicines are presumed to be safe because of their natural origin, consumption of such products may be dangerous due to the content of undeclared drugs, adulteration with multiple substances and contamination with toxic metals.

A local straight-line screening (LSLS) algorithm was recently designed as a method to detect synthetic drug(s) in adulterated herbal medicines based on infrared spectroscopy. Some modifications are made in this paper to improve the existing LSLS algorithm, including interpolation, second derivation, and change of calculation regions from 3 to 7 data points. These modifications have decreased the effect of unpredicted noises and baseline shift on infrared spectroscopy, resulting in outstanding detailed spectral characteristics of the suspected synthetic drugs. The algorithm has been tested using five kinds of synthetic drugs (sibutramine, fenfluramine, lovastatin, sildenafil, and methyldopa) in 40 herbal medicine samples. The concentration of the synthetic drug(s) predicted by the modified LSLS algorithm is closer to those determined by high-performance liquid chromatography. Consequently, the correct results rise from 30 obtained using the original LSLS to 36 obtained using the modified LSLS in 40 samples, the false negative responses drop from 5 to 1, and the false positive responses drop from 5 to 3. The results obtained using the M-LSLS algorithm based on the sibutramine spectrum collected at different times and on different instruments also vary within acceptable ranges. These allow the method to be more appropriate for the preliminary screening of herbal medicines suspected of adulteration with synthetic drugs, with high rapidity, accuracy, and cost effectiveness.

Objective: The aim of this study was to evaluate the quality and quantity of drug information available to consumers on Internet websites marketing herbal weight-loss dietary supplements in the United States. Methods: We conducted an Internet search using the search engines Yahoo and Google and the keywords "herbal weight loss." Website content was evaluated for the presence of active/inactive ingredient names and strengths and other Food and Drug Administration (FDA) labeling requirements. Information related to drug safety for the most common herbal ingredients in the products evaluated was compared against standard herbal drug information references. Results: Thirty-two (32) websites were evaluated for labeling requirements and safety information. All sites listed an FDA disclaimer statement and most sites (84.4%) listed active ingredients, although few listed strengths or inactive ingredients. Based on the drug information for the most common ingredients found in the weightloss dietary supplements evaluated, potential contraindications for cardiovascular conditions, pregnancy/nursing, and high blood pressure were listed most frequently (73%, 65.5%, and 37%, respectively), whereas few websites listed potential drug interactions or adverse reactions. Conclusions: Potential hazards posed by dietary supplements may not be accurately, if at all, represented on Internet websites selling these products. Since consumers may not approach their physicians or pharmacists for information regarding use of dietary supplements in weight loss, it becomes necessary for health care providers to actively engage their patients in open discussion regarding the use, benefits, and hazards of dietary supplements.

In several studies it has been demonstrated that products containing pharmaceutically active ingredients are marketed as dietary supplements. Most of these products contain anabolic steroids. Recently products for weight loss containing active drugs have also appeared on the market. In the present case a healthy male ordered the product 'Anabolic burner' via the Internet. The product was received from a German dispatcher and paid by bank transfer to a German bank account. After ingesting one tablet he reported tremor and delivered a urine sample. This urine was found to contain 2 ng/mL of clenbuterol utilizing LC-MS/MS analysis. Additionally the product itself was analyzed with GC-MS for clenbuterol, yielding a content of about 30 microg per tablet. The beta-2 agonist clenbuterol is only legally available on prescription and is classified as prohibited doping substance in sports. The present case for the first time confirms the presence of clenbuterol in a dietary supplement. It again demonstrates the common problem with products on the supplement market, where non-licensed pharmaceuticals and doping substances are easily available. The ingestion of these products containing additions of therapeutic drugs can lead to side effects and/or interactions with conventional medicines. Copyright (c) 2007 John Wiley & Sons, Ltd.

Problem of adulteration of herbal medicines with synthetic drugs is getting a common and dangerous phenomenon in Poland. The purpose of this study was the qualitative estimation of content of the Chinese herbal medicine for slimming "Meizitanc" as well as the estimation of hazard for human health and life. Twenty herbal packages which were secured by police in the 2006 year were investigated. The main ingredient of herbal medicine "Meizitanc" was sibutramine. The average mass of sibutramine hydrochloride in the "Meizitanc" capsule was about 10 mg. Additionally the trace amount of xylene and a starch were detected in the capsules. The presence of mentioned above substances were confirmed by different analytical methods like: gas chromatography with mass spectrometry GC/MS, thin layer chromatography TLC, high-pressure liquid chromatography HPLC/UV-DAD and infrared spectrometry IR. There were not determined any herbal-originated substances, which were mentioned on the packages. It was not found any pharmacologically active substance in one of the twenty examined packages. Conclusions: The medicine containing sibutramine should be used under the strict medical control. For safety of the patients all herbal products should be buy from authorized her

In America, recent growth in the popularity of Chinese herbal/patent medicines (CHM/CPM) has generated concerns as to the safety of these and other herbal remedies. Lack of strict federal regulations has lead to the possibility of improper labeling and even adulteration of these products with western drugs or other chemical contaminants. Our laboratory has conducted an analytical study to determine the presence of undeclared pharmaceuticals and therapeutic substances within CHM/CPM sold in New York City's Chinatown. Ninety representative samples randomly purchased in the form of pills, tablets, creams and teas were screened by appropriate analytical techniques including TLC, GC/MS and HPLC. Five samples contained nine different western pharmaceuticals. Two of these samples contained undeclared or mislabeled substances. One sample contained two pharmaceuticals contraindicated in people for whom the product was intended. Drugs identified include promethazine, chlormethiazole, chlorpheniramine, diclofenac, chlordiazepoxide, hydrochlorothiazide, triamterene, diphenhydramine and sildenafil citrate (Viagratrade mark).

ABSTRACT: BACKGROUND: Many people now seek alternative methods of weight loss. The internet provides a readily available source of weight reduction products, the ingredients of which are often unclear. The authors describe a case of acute hepatitis in a 20 year old woman caused by such a product purchased over the internet. Case Presentation A 20-year old woman presented with a two day history of abdominal pain, vomiting and jaundice. There were no identifiable risk factors for chronic liver disease. Liver function tests demonstrated an acute hepatitis (aminoaspartate transaminase 1230 IU/L). A chronic liver disease screen was negative. The patient had started a weight loss product(Pro-Lean), purchased over the internet two weeks prior to presentation. The patient was treated conservatively, and improved. The sequence of events suggests an acute hepatitis caused by an herbal weight loss product. CONCLUSION: This case report highlights the dangers of weight loss products available to the public over the internet, and the importance of asking specifically about alternative medicines in patients who present with an acute hepatitis.