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Forensic Science International Jul 2024The use of controlled precursors for reaction optimisation is not always practical. One approach to limiting the use of controlled substances is to instead use 'model...
The use of controlled precursors for reaction optimisation is not always practical. One approach to limiting the use of controlled substances is to instead use 'model compounds'. Herein, two model compounds resembling norephedrine and ephedrine were selected based on their (i) structural similarity (i.e., presence of key functional groups) and (ii) availability from multiple suppliers without restriction. Model compounds 2-amino-1-phenylethanol and 2-(methylamino)-1-phenylethanol (halostachine), were compared to norephedrine and pseudoephedrine by firstly subjecting them to transformations known in the synthesis of amphetamines, and secondly, comparing the compounds using colourimetric spot tests, FTIR and NMR.
Topics: Spectroscopy, Fourier Transform Infrared; Amphetamines; Magnetic Resonance Spectroscopy; Central Nervous System Stimulants; Humans; Ephedrine; Colorimetry; Phenylpropanolamine; Pseudoephedrine; Models, Chemical
PubMed: 38781837
DOI: 10.1016/j.forsciint.2024.112062 -
Forensic Science International Jul 2024In previous work, a novel pathway for the synthesis of ephedrine/pseudoephedrine and methamphetamine using the precursors benzaldehyde, nitroethane and dimethyl...
In previous work, a novel pathway for the synthesis of ephedrine/pseudoephedrine and methamphetamine using the precursors benzaldehyde, nitroethane and dimethyl carbonate was investigated, and an impurity profile presented. This paper presents chiral and stable isotope ratios of ephedrine/pseudoephedrine and methamphetamine synthesised by this pathway. Based on the chiral profile and the more negative δC (avg. -33.2‰) and more positive δH values, it is possible to distinguish ephedrine/pseudoephedrine and methamphetamine prepared from this pathway from those of "fully synthetic", "semi-synthetic" or "natural" origin. The more positive δH values of methamphetamine from this pathway allowed for differentiation from methamphetamine produced from phenyl-2-propanone. It was noted, however, that the use of stable isotope profiling would likely be limited when a benzaldehyde source having a negative δH value was used as a precursor. Furthermore, the stable isotope values alone could not be used to differentiate from methamphetamine prepared by the Akabori-Momotani reaction, highlighting the need for combination with impurity profiling.
PubMed: 38776711
DOI: 10.1016/j.forsciint.2024.112063 -
Journal of Analytical Toxicology May 2024In forensic toxicology, the pediatric population requires special focus when evaluating positive findings because of the many toxicokinetic and toxicodynamic differences...
In forensic toxicology, the pediatric population requires special focus when evaluating positive findings because of the many toxicokinetic and toxicodynamic differences (e.g., metabolic capabilities, body size, etc.) between the pediatric and adult populations. In particular, the administration of over-the-counter (OTC) medications needs careful consideration, as dosages given to the pediatric population (0 days - 18 years), particularly those given to individuals less than five years of age, tend to be lower than those given to individuals closer to adulthood. Postmortem pediatric data from eleven years (2010-2020) was compiled. A total of 1413 positive cases contained one or more of the following common OTC medications: antihistamines (brompheniramine, chlorpheniramine, diphenhydramine, doxylamine, and pheniramine), pain relievers (acetaminophen, naproxen, ibuprofen, and salicylates), cold/flu medications (dextro/levomethorphan, guaifenesin, ephedrine, and pseudoephedrine), gastrointestinal (GI) aids (dicyclomine and loperamide), and/or sleep aids (melatonin). Antihistamines, cold/flu medications, and pain relievers are the most common classes of drugs encountered in the postmortem pediatric population. To evaluate trends, three main age groups were created: ≤5 years old (5U, birth-5 years old), middle childhood (MC, 6-11 years old), and early adolescence (EA, 12-18 years old). When considering the data, it must be noted that many of these drugs may be co-administered in single and/or multi-drug formulations. In addition, some drugs may have a variety of uses, e.g., antihistamines may also be used as sleep aids. Of note, the prevalence of cases involving those aged 6-11 years old was far less than their younger and older pediatric counterparts. With the widespread availability of OTC medications, unintentional overdoses, recreational misuse, and suicidal overdoses can occur in the vulnerable, pediatric population.
PubMed: 38771225
DOI: 10.1093/jat/bkae042 -
Neuro-ophthalmology (Aeolus Press) 2024Ma Huang (), a traditional herbal remedy, which contains pseudoephedrine and ephedrine, has sympathomimetic characteristics. Despite being banned by the Federal Drug...
Ma Huang (), a traditional herbal remedy, which contains pseudoephedrine and ephedrine, has sympathomimetic characteristics. Despite being banned by the Federal Drug Administration in 2004, it is still used for weight loss and energy boosting in some countries. A previous healthy 42-year-old woman experienced sudden blurred vision in both eyes. Her pupils were dilated to 6 mm each, showing diminished light reflex responses, and were not responsive to both 0.1% and 1% pilocarpine. The day before the onset of her symptoms she had taken a herbal supplement. The woman's herbal medicine was believed to contain ephedrine, a component found in Ma Huang. The sympathomimetic effects of this substance could potentially induce mydriasis. After discontinuing the medication, her symptoms improved over 4 days, leading to a suspicion of drug-induced bilateral mydriasis. Herbal products prescribed for weight loss, which may contain potential elements such as Ma Huang, could lead to unforeseen side effects like bilateral mydriasis, and should be appropriately highlighted.
PubMed: 38756336
DOI: 10.1080/01658107.2023.2301363 -
ACS Omega Apr 2024Traditional Chinese medicine (TCM) formula decoctions easily form nanoaggregates due to self-assembly during the decoction process. However, research on nanoaggregates...
Traditional Chinese medicine (TCM) formula decoctions easily form nanoaggregates due to self-assembly during the decoction process. However, research on nanoaggregates in TCM is still in its infancy with limited systematic studies. Maxing Shigan Decoction (MXSGT), a TCM formula, has been commonly used for the treatment of fever for thousands of years in China. This study used MXSGT as an example to investigate the antipyretic effects of MXSGT nanoaggregates (MXSGT-NAs) in its decoction, shedding light on the compatibility mechanisms of Chinese medicine. MXSGT-NAs were isolated by using high-speed centrifugation and dialysis techniques. The morphology, particle size distribution, and electrical potential of MXSGT-NAs were characterized. High-performance liquid chromatography (HPLC) was used to detect ephedrine and pseudoephedrine in MXSGT-NAs. The self-assembly mechanism of MXSGT-NAs was investigated by deconstructing the prescription. In pharmacodynamic experiments, a rat fever model was established through the subcutaneous injection of dry yeast to investigate the antipyretic effects of MXSGT-NAs. The results showed the presence of regularly shaped spherical nanoaggregates in MXSGT. It contains carbon, oxygen (O), sulfur (S), sodium, aluminum (Al), calcium (Ca), iron, magnesium, bismuth (Bi), etc. MXSGT-NAs exerted substantial antipyretic effects on febrile rats. Furthermore, we found micrometer-sized particles composed of Ca, O, S, potassium, and Bi in Shi gao decoctions. This study is the first to provide evidence for the self-assembling property of Shi gao, elucidate the scientific connotation of dispensing Shi gao in MXSGT, and provide a novel perspective for the study of TCM decoctions.
PubMed: 38708238
DOI: 10.1021/acsomega.4c00423 -
Oxford Medical Case Reports Apr 2024Erythromelalgia is a rare, highly debilitating disorder characterised by severe episodes of discomfort, erythema, and desquamation of the extremities. Its causes include...
OBJECTIVE
Erythromelalgia is a rare, highly debilitating disorder characterised by severe episodes of discomfort, erythema, and desquamation of the extremities. Its causes include genetic factors, medications, and several underlying medical conditions. This paper describes a novel cause of erythromelalgia through a case report and literature review.
CASE DESCRIPTION
A 47-year-old Caucasian man presented with a two-year history of intermittent pain, redness and desquamation of the hands. He experienced several such episodes, each lasting 3-4 weeks. A skin biopsy confirmed the diagnosis of erythromelalgia. After several recurrences, he admitted to the intermittent use of pseudoephedrine as a nasal decongestant, which coincided with the episodes of erythromelalgia. Complete resolution of symptoms was reported on cessation of this medication.
CONCLUSION
Pseudoephedrine has been reported to cause a wide range of cutaneous reactions but has not been known to precipitate erythromelalgia. Recognition of this rare side effect may offer early diagnosis and reduced morbidity.
PubMed: 38680776
DOI: 10.1093/omcr/omae037 -
Journal of Chromatography. A May 2024Epimer separation is crucial in the field of analytical chemistry, separation science, and the pharmaceutical industry. No reported methods could separate simultaneously...
Epimer separation is crucial in the field of analytical chemistry, separation science, and the pharmaceutical industry. No reported methods could separate simultaneously epimers or even isomers and remove other unwanted, co-existing, interfering substances from complex systems like herbal extracts. Herein, we prepared a heptapeptide-modified stationary phase for the separation of 1R,2S-(-)-ephedrine [(-)-Ephe] and 1S,2S-(+)-pseudoephedrine [(+)-Pse] epimers from Ephedra sinica Stapf extract and blood samples. The heptapeptide stationary phase was comprehensively characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The separation efficiency of the heptapeptide column was compared with an affinity column packed with full-length β-AR functionalized silica gel (β-AR column). The binding affinity of the heptapeptide with (+)-Pse was 3-fold greater than that with (-)-Ephe. Their binding mechanisms were extensively characterized by chromatographic analysis, ultraviolet spectra, circular dichroism analysis, isothermal titration calorimetry, and molecule docking. An enhanced hydrogen bonding was clearly observed in the heptapeptide-(+)-Pse complex. Such results demonstrated that the heptapeptide can recognize (+)-Pse and (-)-Ephe epimers in a complex system. This work, we believe, was the first report to simultaneously separate epimers and remove non-specific interfering substances from complex samples. The method was potentially applicable to more challenging sample separation, such as chiral separation from complex systems.
Topics: Ephedrine; Pseudoephedrine; Receptors, Adrenergic, beta-2; Molecular Docking Simulation; Ephedra sinica; Chromatography, High Pressure Liquid; Plant Extracts; Humans; Stereoisomerism; Oligopeptides
PubMed: 38569445
DOI: 10.1016/j.chroma.2024.464857 -
Journal of Chromatographic Science Mar 2024This study reports the development of an effective high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the quantification of two...
This study reports the development of an effective high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the quantification of two analogs of rosmarinic acid (RA) in rat plasma, namely methyl (E)-2-(3-(3,4-difluorophenyl)acrylamido)-3-(3,4-dihydroxyphenyl)propanoate (A11) and methyl (E)-3-(3,4-dihydroxyphenyl)-2-(3-(3,4-dihydroxyphenyl)acrylamido)propanoate (A2). These analogs, featuring N atoms instead of O atoms, exhibit enhanced bioavailability and distinct pharmacological activities compared with RA. The HPLC separation was carried out on a C18 column (1.9 μm, 2.1 mm × 100 mm) coupled with a security guard C18 column (5 μm, 2.1 mm × 10 mm). A triple-quadrupole mass spectrometer equipped with an electrospray ionization ion source was utilized for ion generation. Pseudoephedrine hydrochloride was utilized as a standard, and a single-step protein precipitation method using isopropanol:ethyl acetate (v/v, 20:80) was employed for sample pretreatment. The developed method demonstrated excellent linearity over the concentration range of 5-750 ng/ml for both A11 and A2, with relative standard deviations of <15% and relative errors within 15% during daily course analysis. The method allowed for the unambiguous quantification and identification of A11 and A2 in vivo. The results of this study provide a meaningful foundation for evaluating the clinical applications of these analogs.
PubMed: 38520038
DOI: 10.1093/chromsci/bmae009 -
Journal of Infection and Public Health May 2024The common cold is one of the most frequently occurring illnesses worldwide. The aim of this study was to determine which OTC anti-common cold medications were most...
BACKGROUND
The common cold is one of the most frequently occurring illnesses worldwide. The aim of this study was to determine which OTC anti-common cold medications were most often recommended by pharmacists and if the COVID-19 pandemic affected such recommendations.
METHODS
Non-interventional, observational research trial using a self-developed questionnaire to collect data on pharmacists' recommendations for anti-common cold OTC treatment. The data were collected during the COVID-19 pandemic (December 2021-February 2022) in four large community network pharmacies in Lodz (Poland) and then compared with an analogue period of time before the pandemic (December 2019-February 2020).
RESULTS
During COVID-19 pandemic there was a significant (p < 0.05) reduction in paracetamol, acetylsalicylic acid, metamizole magnesium, inosines, alpha-mimetics, mucolytics, homeopathics, and sore throat products and an increase in other tablets/capsules and add-on product recommendations. There was a significant relationship (p < 0.05, OR > 1) between the recommended frequency of paracetamol, inosines, sore throat products (each symptom), metamizole magnesium (headache, fever), acetylsalicylic acid (headache, fever, fatigue), NSAIDs, alpha-mimetics (headache, rhinorrhea), pseudoephedrine (rhinorrhea), homeopathics (headache), herbal products (fatigue), antihistamines (rhinorrhea, cough), and mucolytics (headache, fever, cough).
CONCLUSIONS
Favorable prices (before COVID-19 pandemic) and reports on common NSAIDs side effects (beginning of the pandemic) led to high sale of paracetamol. Increased awareness of clinical effectiveness of some medications or their reduced availability influenced their limited recommendations.
Topics: Humans; Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Common Cold; Cough; COVID-19; Expectorants; Headache; Nonprescription Drugs; Pandemics; Pharmacists; Pharyngitis; Rhinorrhea
PubMed: 38518682
DOI: 10.1016/j.jiph.2024.03.001