Development and Validation of an HPLC Method for Simultaneous Determination of Capsaicinoids and Camphor in Over-the-Counter Medication for Topical Use.

A reverse-phase high-performance liquid chromatography method was developed to determine and quantify capsaicin (trans-8-methyl-N-vanillyl-6- nonenamid), dihydrocapsaicin (8-methyl-N-vanillylnonanamide), and camphor (trimethylbicyclo[2.2.1]heptan-2-one). It is applicable in analyses of over-the-counter (OTC) medications for topical use and raw materials such as chili pepper oleoresin. Chromatographic separation was carried out on a C18 column using an isocratic flow of the mobile phase containing acetonitrile and ultrapure water in a ratio of 2:3, with pH adjusted to 3.2 using glacial acetic acid, and a flow rate of 1.5 mL/min. The concentration of the eluting compounds was monitored by a diode-array detector at a wavelength of 281 nm. The method was evaluated for several validation parameters, including selectivity, accuracy (confidence intervals < 0.05%), repeatability, and intermediate precision. The limit of detection (LOD) was determined to be 0.070 µg/mL for capsaicin, 0.211 µg/mL for dihydrocapsaicin, and 0.060 µg/mL for camphor. The limit of quantification (LOQ) was determined to be 0.212 µg/mL for capsaicin, 0.640 µg/mL for dihydrocapsaicin, and 0.320 µg/mL for camphor. Linearity was set in the range of 2.5-200 µg/mL for capsaicin and dihydrocapsaicin and 25-2000 µg/mL for camphor. The suggested analytical method can be used for quality control of formulated pharmaceutical products containing capsaicinoids, camphor, and propolis.

Study on Chinese patent medicine based on major component analysis and quality control evaluation: A case study of Jizhi Syrup.

Jizhi Syrup (JZS) is a popular Chinese patent medicine (CPM) for the treatment of respiratory diseases in clinical practice, especially acute or chronic bronchitis. JZS is a complex formula composed of 8 kinds of herbs and lack of comprehensive researches on chemical components. To further define its components, ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS) and headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) were utilized to identify and classify the chemical components of JZS. A total of 178 chemical compounds encompassing the 8 herbs of JZS were identified and the chemical components were comprehensively explicit. It made up for the gap that volatile components were not studied in the previous study. Based on this, a new method for the quality control of JZS based on its characteristic components was established by fingerprints, multi-component quantitative analysis and quantity transfer of JZS. A dual-wavelength high-performance liquid chromatography (HPLC) fingerprints were established at 210 nm and 260 nm. Four volatile components (linalool, bornyl acetate, 2-undecanone and α-terpineol) and eight nonvolatile components (ephedrine hydrochloride, protocatechuic acid, 5-caffeoylquinic acid, 4-hydroxybenzoic acid, naringin, neohesperidin, glycyrrhizic acid and praeruptorin A) were quantitated by HS-SPME-GC-MS and HPLC-diode array detection (DAD). Meanwhile, six exclusive nonvolatile components were studied for the quantity transfer of Herbs-Intermediate-CPM and all the transfer rates were between 55.23% and 89.20%. This study is the first comprehensive study of the major components in JZS, and its results can be useful to standardize the quality control and provide a valuable reference for other CPMs.

Drug Shop Intervention to Enhance Knowledge, Attitude, and Practices of Patent Medicine Vendors for the Control of COVID-19 In Southeastern Nigeria.

Drug shops are the first point of care for most community members in low-resource countries. Because of symptomatic similarities with common illnesses such as malaria, probable coronavirus disease 2019 (COVID-19) cases may seek care at drug shops, where the knowledge and skills required to handle it may be lacking, thereby fostering community spread of the disease. This single-arm study provided an intervention to improve COVID-19-related knowledge, attitude, and practices of patent medicine vendors (PMVs) in 97 participating drug shops selected through cluster sampling in Owerri, southeastern Nigeria. The intervention involved a drug shop sensitization using information, education, and communication material, as well as training on the use of a risk assessment checklist to identify probable COVID-19 cases and to take appropriate action. Data were collected to determine the effect of this intervention using a pre-tested questionnaire and practice observation checklist, first at baseline and then 3 months post-intervention. Data analysis involved exploratory analysis and the t-test to determine pre- and post-intervention mean score differences at the 5% α level. There was post-intervention knowledge improvement on the COVID-19 causative pathogen (98.1% post-intervention versus 61.9% pre-intervention) and disease transmissibility from person to person (95.9% post-intervention versus 81.4% pre-intervention) among other knowledge domains. There was significant post-intervention improvement for positive attitude, with a mean gain score of 2.8 ± 1.7 (t = 4.4, P = 0.005), and preventive practices, with a mean gain score of 6.0 ± 4.7 (t = 4.1, P = 0.007). Engaging patent medicine vendors in the pandemic response plans through targeted interventions such as drug shop intervention could prove vital in the fight against COVID-19.

An Analysis for Adulteration and Contamination of Over-the-Counter Weight-Loss Products.

Six Australian and five overseas complementary medicines (CM) and meal replacement shake products were analysed for potential adulteration with two common active pharmaceutical ingredients, caffeine and sibutramine, using thin-layer chromatography and mass spectrometry. The declared amount of caffeine in each product was also reviewed. Finally, the products were examined for heavy metal contamination using inductively coupled plasma-mass spectrometry. The results showed that there was no detected adulteration of either caffeine (for those products that did not list caffeine as an ingredient) or sibutramine in the 11 products; however, based on the product labels, one Australian and one overseas (two in total) CM product contained more than the maximum daily safety limit (400 mg) of caffeine. Potentially excessive lead and/or chromium was detected in six products, including four Australian products and two products purchased online. One Australian CM product appeared to contain these heavy metals at concentrations at, or exceeding, the safety limits specified in the United States Pharmacopeia or set by the World Health Organization. The overconsumption of caffeine and heavy metals has the potential of causing significant health effects in consumers.

Simultaneous determination of seven compounds in Chinese patent medicines Chenxiangqu by matrix solid-phase dispersion coupled with ultra high performance liquid chromatography and quadrupole time-of-flight mass spectrometry.

A simple, efficient, and sensitive strategy by coupling matrix solid-phase dispersion with ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry was proposed to extract and determine three types of components (including seven analytes) in Chinese patent medicines Chenxiangqu. The highly ordered mesoporous material Fe-SBA-15 synthesized under weakly acidic conditions was selected as a dispersant in matrix solid phase dispersion extraction for the first time. Several parameters including the mass ratio of sample to dispersant, the type of dispersant, the grinding time, and the elution condition were investigated in this work. Under the optimized conditions, 20 compounds were identified by quadrupole time-of-flight mass spectrometry and seven analytes were quantified. The results demonstrated that the developed method has good linearity (r > 0.9995), and the limits of detection of the analytes were as low as 0.55 ng/mL. The recoveries of all seven analytes ranged from 97.6 to 104.6% (relative standard deviation < 3.4%). Finally, the improved method was successfully applied to determination of five batches of Chenxiangqu samples, which provided a robust method in quality control of Chinese patent medicines Chenxiangqu. The developed strategy also shows its great potential in analysis of complex matrix samples.

Smart Spectral Processing of Data for the estimation of Commonly Used Over-the-counter (OTC) Co-formulated drug; Pseudoephedrine hydrochloride and Ibuprofen.

Oral pharmaceutical preparation containing pseudoephedrine hydrochloride (PSE) and ibuprofen (IBU) is widely prescribed as over- the- counter (OTC) for treatment of common cold-sinus. Development of four precise and accurate spectrophotometric methods are established for the concurrent determination of (PSE) and (IBU)in this preparation exploiting zero and/or ratio spectra. Method I is a dual wavelength method (DW). method II is a ratio difference method (RD), method III is a constant multiplication coupled with spectrum subtraction method (CM-SS) and method IV is a constant center coupled with spectrum subtraction method (CC-SS). While, absorbance correction method (AC) is successfully established for the determination of (IBU) only exploiting zero order absorption spectra. The calibration curves are linear over the concentration range of 100.0-900.0 µg/mL for (PSE) and 200.0-1000.0 µg/mL for (IBU). No separation steps are required for the spectrophotometric procedures which augments their simplicity. Analyzing synthetic mixtures of the cited drugs evaluated the specificity of the applied methods. Validation of the analysis results have been statistically performed confirming the accuracy and reproducibility of the proposed method through recovery studies which were carried out by following ICH guidelines. Thus, the developed methods can be successfully applied routinely in quality control laboratory.

Modified Magnetic Nanoparticle-Based Solid-Phase Extraction for the Determination of Trace Amounts of Aflatoxins B1 and B2 in Chinese Patent Medicines: The Use of Fupuganmao Granules as a Case Study.

Background: Aflatoxins (AFs) have attracted increasing amounts of attention in recent years for their high toxicity. Previously, AF-polluted Chinese Patent Medicines (CPMs) were ignored, but their quality, safety, and efficacy might be influenced by the toxic compounds. Objective: The objective is to develop a simple, low-cost, and efficient method for quantitative analysis of aflatoxins B1 (AFB1) and B2 (AFB2) in CPMs to ensure their safe use. Methods: A simple, modified, magnetic nanoparticle-based solid-phase extraction (SPE) combined with HPLC-fluorescence detection for the determination of trace amounts of AFB1 and AFB2 was established. The main parameters affecting the efficiency of modified magnetic nanoparticle-based SPE, such as pH of sample solution, adsorbent amount, adsorption time, and desorption condition, were investigated. Results: Under the optimum conditions, AFB1 and AFB2 were linear in the ranges of 0.3-10 and 0.04-3 ng/mL with the correlation coefficient (R) of 0.9998 and 0.9999, respectively. Their intraday precisions were 1.16 and 2.30% and the interday precisions were 1.28 and 1.87% for AFB1 and AFB2, respectively. The developed SPE was applied for AFB1 and AFB2 extraction in three commercially available Fupuganmao granule samples, and the results were compared with the official immunoaffinity column chromatography method. Conclusions: The method provided a preferable candidate for the determination approach of AF measurement in CPMs. Highlights: Amine-functionalized magnetic nanoparticles were successfully applied to SPE for adsorbing AFB1 and AFB2 in CPMs for the first time.

Over-the-Counter Herbal Weight Loss Supplements in Egypt: Label Claim, Microbiological and Pharmaceutical Quality, and Safety Assessments.

OBJECTIVES: Nutraceuticals are advertised and sold with the label claim of being natural and safe herbal products. Due to the absence of clear regulations and guidelines for safety assessments of these products, nutraceuticals are commonly adulterated in order to increase sales. The objective of the current study was to design a comprehensive evaluation system to assess the safety, efficacy, authenticity according to label claim, and pharmaceutical quality of herbal slimming products in between 2015 and 2017. METHODS: We designed a comprehensive assessment system to evaluate the safety, authenticity according to label claim, and pharmaceutical quality of slimming nutraceuticals. Six different popular products were evaluated (Zotreem Plus®, Zotreem Extra®, Malaysian Super Slim®, AB Slim®, Chinese Super Slim®, and Metabolites®). The pharmaceutical evaluation included analyzing the samples via high-performance liquid chromatography to determine any possible adulterants. Additionally, the products' physical properties were assessed via pharmacopeial tests. Finally, a microbial evaluation and a cross-sectional observational retrospective prevalence study were conducted to assess the products' safety and efficacy. -Results: The tested products were found to be adulterated with unreported active pharmaceutical ingredients such as sibutramine, sildenafil, phenolphthalein, and orlistat. Furthermore, they contained heterogeneous amounts of adulterants and exhibited an unsatisfactory pharmaceutical and microbial quality. Finally, the observational survey conducted on users showed that high percentages of participants suffered from common side effects such as depression, diarrhea, and hypertension. CONCLUSIONS: These products threaten the health of consumers. There is a need to raise awareness of the lethal consequences of illegal nutraceuticals.

Nutritional supplements with omega 3 in retinal disease: Relationship between volume and concentration in commercial products. / Suplementación nutricional con omega 3 en retina: relación entre volumen y concentración en productos comerciales.

OBJECTIVE: To analyse the morphometric characteristics and the concentration of (docosahexaenoic acid) DHA and eicosapentaenoic acid (EPA) of the different nutritional supplements with omega 3 available on the market for retinal disease. MATERIAL AND METHODS: A double-blind study was conducted with a single observer, of the different omega 3 supplementation tablets sample marketed in Spain. The length of the tablet, the concentration of omega 3 in total, as well as DHA and EPA were studied separately using the amount provided by the manufacturer and the volume of the capsule calculated from the development of a specific formula for it. RESULTS: A total of 10 different nutritional supplements were included. The mean of total omega 3, DHA and EPA was 383.10±160.90, 210.72±93.3, and 112.34±140.98mg, respectively. The mean size of the capsules was 14.77±0.19×8.13±0.09mm The smallest sized capsule was that of Oftan macula omega® (Esteve, Barcelona, Spain). Brudymacula® (Brudylab, Barcelona, Spain) and Brudyretina 1.5 g® (Brudylab, Barcelona, Spain) tablets contained more DHA, with Nutrof omega® (Thea Laboratories, Barcelona, Spain) having the lowest concentration of omega 3, DHA and EPA, per tablet. CONCLUSION: There are significant differences in size, volume, quantity, and concentration of omega 3 and its derivatives, between different commercial preparations. Only the knowledge of the characteristics of the nutritional supplements will enable us to provide a more personalised indication of their use for our patients.

Differences in drug quality between South Africa and Germany.

OBJECTIVES: To examine differences in drug product quality between products marketed in developed countries and in developing countries. METHODS: The quality of drug products marketed in both Germany and South Africa by the same pharmaceutical company was compared. A fixed-dose combination tablet containing amoxicillin/clavulanic acid, and mometasone furoate nasal spray were selected to represent generic medicines requiring prescriptions, while skin lightening products (legally obtained and/or confiscated) were selected to represent pharmaceutical products that are available without a prescription. Pharmacopoeial tests included assay, content uniformity, and where applicable, dissolution in addition to a visual examination of the packaging. KEY FINDINGS: Some differences between the product marketed in Germany and in South Africa were detected for the amoxicillin tablet formulations, although all samples still complied with regulatory requirements. The mometasone nasal spray product marketed in South Africa delivered a higher dose than was declared on the label. The composition of the skin lightening products conformed qualitatively with labelling, but in some South African samples alarmingly high amounts of hydroquinone were found. CONCLUSIONS: Important differences in quality were detected between some German and South African products. To preclude drug products of poor or doubtful quality from entering the market in South Africa, countermeasures are needed.

Prevalence of xenobiotic substances in first-trimester blood samples from Danish pregnant women: a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate the prevalence of xenobiotic substances, such as caffeine, nicotine and illicit drugs (eg, cannabis and cocaine), in blood samples from first-trimester Danish pregnant women unaware of the screening. DESIGN: A cross-sectional study examined 436 anonymised residual blood samples obtained during 2014 as part of the nationwide prenatal first-trimester screening programme. The samples were analysed by ultra performance liquid chromatography with high-resolution time-of-flight mass spectrometry. SETTING: An antenatal clinic in a Danish city with 62 000 inhabitants, where >95% of pregnant women joined the screening programme. PRIMARY AND SECONDARY OUTCOME MEASURES: The prevalence and patterns of caffeine, nicotine, medication and illicit drug intake during the first trimester of pregnancy. RESULTS: The prevalence of prescription and over-the-counter drug detection was 17.9%, including acetaminophen (8.9%) and antidepressants (3.0%), of which citalopram (0.9%) was the most frequent. The prevalence of illegal drugs, indicators of smoking (nicotine/cotinine) and caffeine was 0.9%, 9.9%, and 76.4%, respectively. Only 17.4% of women had no substance identified in their sample. CONCLUSIONS: This study emphasises the need for further translational studies investigating lifestyle habits during pregnancy, as well as the underlying molecular mechanisms through which xenobiotic substances may affect placental function and fetal development.

Over-the-Counter "Adrenal Support" Supplements Contain Thyroid and Steroid-Based Adrenal Hormones.

OBJECTIVE: To assess whether dietary supplements that are herbal and/or animal-derived products, marketed for enhancing metabolism or promoting energy, "adrenal fatigue," or "adrenal support," contain thyroid or steroid hormones. METHODS: Twelve dietary adrenal support supplements were purchased. Pregnenolone, androstenedione, 17-hydroxyprogesterone, cortisol, cortisone, dehydroepiandrosterone sulfate, synthetic glucocorticoids (betamethasone, dexamethasone, fludrocortisone, megestrol acetate, methylprednisolone, prednisolone, prednisone, budesonide, and triamcinolone acetonide) levels were measured twice in samples in a blinded fashion. This study was conducted between February 1, 2016, and November 1, 2016. RESULTS: Among steroids, pregnenolone was the most common hormone in the samples. Budesonide, 17-hydroxyprogesterone, androstenedione, cortisol, and cortisone were the others in order of prevalence. All the supplements revealed a detectable amount of triiodothyronine (T3) (63-394.9 ng/tablet), 42% contained pregnenolone (66.12-205.2 ng/tablet), 25% contained budesonide (119.5-610 ng/tablet), 17% contained androstenedione (1.27-7.25 ng/tablet), 8% contained 17-OH progesterone (30.09 ng/tablet), 8% contained cortisone (79.66 ng/tablet), and 8% contained cortisol (138.5 ng/tablet). Per label recommended doses daily exposure was up to 1322 ng for T3, 1231.2 ng for pregnenolone, 1276.4 ng for budesonide, 29 ng for androstenedione, 60.18 ng for 17-OH progesterone, 277 ng for cortisol, and 159.32 ng for cortisone. CONCLUSION: All the supplements studied contained a small amount of thyroid hormone and most contained at least 1 steroid hormone. This is the first study that measured thyroid and steroid hormones in over-the-counter dietary "adrenal support" supplements in the United States. These results may highlight potential risks of hidden ingredients in unregulated supplements.

On-Line two dimensional liquid chromatography based on skeleton type molecularly imprinted column for selective determination of sulfonylurea additive in Chinese patent medicines or functional foods.

Substandard and counterfeit anti-diabetic medicines directly influence the health and impose a great danger to individual patients and to public health. Counterfeiting has become a serious and underreported problem in the pharmaceutical industry. There are a large number of counterfeit medicines flooded in anti-diabetic markets which effect human health directly and indirectly. Therefore, some novel analytical techniques are necessary to be established for detecting these counterfeit drugs. In this study, a novel skeleton type molecularly imprinted column was successfully prepared. Based on the column, a simple, fast and reliable two-dimensional chromatography analytical system was established for selective determination of the illegal sulfonylurea additive in traditional Chinese patent medicines and functional foods. The developed method was validated. The linearitiesof the method were tested with calibration curves using ten calibration points in the concentration range of 0.25-12.5µg/g. The LODs were 0.0125µg/g and 0.01µg/g for tolbutamide and glibenclamide respectively. The five batches of Chinese patent medicines and dietary supplements obtained from different markets and online websites were tested by the validated method. With good retention time and spectral confirmation, chemical anti-diabetic substances were identified and quantified in traditional Chinese medicine and in dietary supplements.

Community pharmacists' perceptions about pharmaceutical service of over-the-counter traditional Chinese medicine: a survey study in Harbin of China.

BACKGROUND: This study aims to investigate community pharmacist's perception on the provision of over-the-counter (OTC) traditional Chinese medicine (TCM) pharmaceutical services; focusing on the areas of their attitude, general practice, perceived barriers and suggested improvements. METHODS: Questionnaire survey targeting community pharmacists in Harbin of China was applied in this study. Questionnaires were distributed and collected at community pharmacies. Data was analyzed by combining descriptive analysis and Chi-test. RESULTS: 280 valid questionnaires were collected, giving a response rate of 78%. Respondents generally showed positive attitude towards OTC TCM pharmaceutical services. However, they were uncertain about whether such pharmaceutical services should be considered as their primary responsibility. Respondents indicated that they acted proactively to find out all the medicines taken by their patients and to remind consumers of possible OTC TCM adverse reactions. However, they were less keen on recommending or re-directing consumers to suitable OTC TCM. The three main barriers hindering the provision of OTC TCM pharmaceutical service identified in this study were "insufficient professional knowledge" (54.6%), "ambiguity of the professional role of pharmacists" (54.6%) and "lack of scientific evidence of OTC TCM" (45.4%). The three main actions considered most relevant to improving pharmaceutical service of OTC TCM were "formulating or refining legislation to clarify the legal and professional role of pharmacists with respect to TCM" (60.7%), "strengthening training of pharmacists with respect to TCM" (57.9%), and "promoting public awareness of the pharmacist's role" (53.6%). According to the results of Chi-test, respondents' perceptions about the attitude, practice, perceived barriers, and improvement suggestions were significantly different depending on the education levels, certificate types and workloads of western medicine. CONCLUSIONS: The community pharmacists in Harbin, China were positive about the provision of OTC TCM pharmaceutical services. However, they were less certain about taking this duty as their primary responsibility. Insufficient knowledge and lack of role definition in the area of OTC TCM were found to be the major factors discouraging the provision of pharmaceutical service on OTC TCM by community pharmacists.

Disposal practices of unused and expired pharmaceuticals among general public in Kabul.

BACKGROUND: Most of the medicine users remain unaware about the disposal of unused or expired medicines. The aim of this study was to know the disposal practices of unused and expired medicines among the general public in Kabul. METHODS: This was a descriptive, cross-sectional survey, conducted through face-to-face interviews using prevalidated structured questionnaire. Returned questionnaires were double-checked for accuracy. Statistical Package for Social Science (SPSS) version 23 was used for statistical analysis. RESULTS: Total of 301 valid questionnaires were returned with a response rate of 100% in which 73.4% men and 26.6% women participated. More than half of the respondents were university graduates. Interestingly, 83.4% of the interviewees purchased medicines on the prescription of which 47.2% were university graduates, while 14.6% purchased medicine over the counter. Among the respondents, 46.5/100 purchased antibiotics and the remaining purchased NSAIDs, anti-hypertensive and anti-diabetic medicines. Significantly, 97/100 checked the expiry date of medicine before buying. Majority (95.3%) of the respondents' stored medicines at home. 77.7% of the respondents discarded the expired medicines in household trash. Majority of respondents held government responsible for creation of awareness for proper medicine disposal. Almost entire sample (98%) felt that improper disposal of unused and expired medicines can affect the environment and health. CONCLUSION: Gaps exist in practices, therefore robust, safe and cost-effective pharmaceutical waste management program supported with media campaign is needed. Healthcare practitioners and community pharmacists should offer training to educate customers on standard medicine disposal practices.

Generic selection criteria for safety and patient benefit [VI]: Comparing the physicochemical and pharmaceutical properties of brand-name, generic, and OTC felbinac tapes.

We measured the pH, water-vapor permeability, adhesive force, peeling-force, elongation rate, support flexibility, and peeling time of medicinal and over-the-counter (OTC) tape preparations containing felbinac. When measuring the pH of each preparation, Felnabion (pH 4.5) was weakly acidic, and EMEC and Tokuon (pH 7.0) were neutral. When measuring the water-vapor permeability of each preparation, that of a generic product, EMEC (380 g/m2/24h), was twice as high as that of a brand-name product, Seltouch (189 g/m2/24 h). The adhesive force was measured using the ball tack test. The adhesive forces of OTC drugs, Salomethyl, Homepass, and Tokuhon (1.04 g), were higher than that of Seltouch (0.06 g). Concerning peeling-force measurement, the peeling-forces of a generic product, Falzy (4.15 N), and an OTC drug, Omuneed (4.89 N), were higher than that of Seltouch (0.91 N). The elongation rates of a generic product, Sumilu (319%), and OTC drugs, Nabolin (298%) and Homepass (299%), were higher than that of Seltouch (251%), but that of Tokuhon (72%) was lower. The support flexibilities of EMEC (150 degrees) and Tokuhon (131 degrees) were higher than that of Seltouch (96 degrees). In addition, the peeling time of Seltouch was 120 min or more, whereas those of EMEC and Nabolin were 1.4 and 0.2 min, respectively. These results suggest that the differences in pharmaceutical properties, such as the pH, water-vapor permeability, adhesive force, peeling-force, elongation rate, support flexibility, and peeling time, among the preparations markedly influence patients' subjective comfortableness. The results of this study facilitated individuals' comfortableness-matched drug selection.

Qualitative and Quantitative Evaluation of Drug and Health Food Products Containing Red Vine Leaf Extracts on the Japanese Market.

Red vine leaf extracts (RVLEs) have traditionally been used for leg wellness and are now standardized to be used as OTC drugs in Europe. In Japan, one brand of RVLE products was recently approved as a direct OTC drug, and RVLEs are still used as ingredients in health food products. Since there is no mandated criterion for the quality of health food products in Japan, the consistent quality and composition of these products are not assured. Here we analyzed OTC drug and health food products containing RVLEs with different lot numbers by LC/MS. Subsequent multivariate analyses clearly indicated that the quality of the health food products was highly variable compared to that of the drug products. Surprisingly, the component contents in the health foods were different even within a same lot in a same brand. The quantitative analyses of flavonols and stilbene derivatives in the drugs and health foods indicated that the concentration of each substance was kept constant in the drugs but not in the health foods. These results strongly indicated that the quality of RVLEs as a whole was not properly controlled in the manufacturing process of health foods. Since RVLE is an active ingredient with pharmaceutical evidences and is used for drugs, the proper regulation for ensuring the consistent quality of RVLEs from product to product would be recommended even in the health foods.

Gold nanoparticles bridging infra-red spectroscopy and laser desorption/ionization mass spectrometry for direct analysis of over-the-counter drug and botanical medicines.

With a coating of gold nanoparticles (AuNPs), over-the-counter (OTC) drugs and Chinese herbal medicine granules in KBr pellets could be analyzed by Fourier Transform Infra-red (FT-IR) spectroscopy and Surface-assisted Laser Desorption/Ionization mass spectrometry (SALDI-MS). FT-IR spectroscopy allows fast detection of major active ingredient (e.g., acetaminophen) in OTC drugs in KBr pellets. Upon coating a thin layer of AuNPs on the KBr pellet, minor active ingredients (e.g., noscapine and loratadine) in OTC drugs, which were not revealed by FT-IR, could be detected unambiguously using AuNPs-assisted LDI-MS. Moreover, phytochemical markers of Coptidis Rhizoma (i.e. berberine, palmatine and coptisine) could be quantified in the concentrated Chinese medicine (CCM) granules by the SALDI-MS using standard addition method. The quantitative results matched with those determined by high-performance liquid chromatography with ultraviolet detection. Being strongly absorbing in UV yet transparent to IR, AuNPs successfully bridged FT-IR and SALDI-MS for direct analysis of active ingredients in the same solid sample. FT-IR allowed the fast analysis of major active ingredient in drugs, while SALDI-MS allowed the detection of minor active ingredient in the presence of excipient, and also quantitation of phytochemicals in herbal granules.

Bromoderma mimicking pyoderma gangrenosum caused by commercial sedatives.

Bromoderma is a rare skin disorder caused by bromide intake. It presents as single or multiple papillomatous nodules or plaques, and ulcers studded with small pustules on the face or limbs. The clinical features of bromoderma are similar to those of pyoderma gangrenosum. A 41-year-old Japanese woman was diagnosed with pyoderma gangrenosum 11 years prior to presentation. Pyoderma had repeatedly appeared over her entire body despite treatment. She also frequently complained of syncopal episodes. She was admitted to our hospital after loss of consciousness and an episode of generalized convulsion. Laboratory tests revealed a negative serum anion gap and hyperchloremia. Her serum bromide level was significantly elevated, suggesting bromide intoxication. The patient had a 10-year history of high serum bromide levels. After the intake of bromide-containing sedatives was stopped, there was no recurrence of pyoderma in the absence of treatment. In conclusion, this case was diagnosed as bromoderma with commercial sedative-induced bromide intoxication. Although the US Food and Drug Administration have banned the use of bromides, over-the-counter (OTC) treatments containing bromides are still used in Japan and other countries. Long-term use of OTC medicines containing bromvalerylurea may result in the development of bromoderma. If unclarified neurological or psychiatric symptoms are associated with pyoderma, we propose measurement of the patient's serum chloride concentration. Determination of hyperchloremia is helpful for the diagnosis of chronic intoxication with bromides.