OBJECTIVE: A pharmacopoeia is a compendium of guidelines and criteria for drug quality. It was established by a national or regional entity and has legal significance. This applies to administration of drugs in a particular nation or region.
METHODS: In this study, the differences and similarities of microbiological acceptance criteria, specifications for microbial enumeration of herbal drugs and herbal drug preparations in 14 national and international pharmacopeias were investigated.
RESULTS: It was found that 12 pharmacopeias have given separate microbial limits for total aerobic microbial count (TAMC) and total yeast and mold count (TYMC), and a list of specified microorganisms for which acceptance criteria are defined. However, similarities were noticed in Ph.Eur, Ph. Helv and, BP. Salmonella, and Escherichia coli are the most common pathogens specified for herbal preparations in which boiling water is added prior to use and for internal use in all Pharmacopoeias because they serve as indicators of potential contamination.
CONCLUSIONS: From this study, it can be concluded that the differences in microbial limit tests and their acceptance criteria as specified in the various pharmacopoeias need to be harmonized. It will become a more convenient option for global drug manufacturers to import/export herbal drugs, and this would also eliminate the burden of performing various analytical methods and comply with different microbial acceptance criteria set by various pharmacopoeias. The comparative data obtained from this study will be used to develop strategies for revisions of pharmacopoeias in a harmonized manner with respect to microbiological acceptance criteria, specifications for microbial enumeration of herbal drugs and herbal drug preparations.

Oxidative stress contributes to impairment of skin health, the wound healing process, and pathologies such as psoriasis or skin cancer. Five Polynesian medicinal plants, among the most traditionally used for skin care (pimples, wounds, burns, dermatoses) are studied herein for their antioxidant properties: Calophyllum inophyllum, Gardenia taitensis, Curcuma longa, Cordia subcordata, and Ficus prolixa. Plant extracts were submitted to in vitro bioassays related to antioxidant properties and their bioactive constituents were identified by a metabolomic analytical approach. High performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) analysis was performed leading to the characterization of 61 metabolites. Compounds annotated for F. prolixa and C. subcordata extracts were reported for the first time. Antioxidant properties were evaluated by total phenolic content (TPC), free radical scavenging DPPH (1,1-diphenyl-2-picryl-hydrazyl), and Ferric Reducing Antioxidant Power activity (FRAP) assays. F. prolixa extract was the most active one and showed antioxidant intracellular activity on keratinocytes by Anti Oxydant Power 1 assay. Online HPLC-DPPH allowed the identification of phenolic bioactive compounds such as quercetin-O-rhamnoside, rosmarinic acid, chlorogenic acid, procyanidins, epicatechin, 5-O-caffeoylshikimic acid, and curcumin as being responsible for the scavenging properties of these plant extracts. These results highlight the potential of F. prolixa aerial roots as a source of antioxidants for skin care applications.

BACKGROUND: Patients hospitalized for a given condition may be receiving other treatments for other contemporary conditions or comorbidities. The use of such observational clinical data for pharmacological hypothesis generation is appealing in the context of an emerging disease but particularly challenging due to the presence of drug indication bias.
OBJECTIVE: With this study, our main objective was the development and validation of a fully data-driven pipeline that would address this challenge. Our secondary objective was to generate pharmacological hypotheses in patients with COVID-19 and demonstrate the clinical relevance of the pipeline.
METHODS: We developed a pharmacopeia-wide association study (PharmWAS) pipeline inspired from the PheWAS methodology, which systematically screens for associations between the whole pharmacopeia and a clinical phenotype. First, a fully data-driven procedure based on adaptive least absolute shrinkage and selection operator (LASSO) determined drug-specific adjustment sets. Second, we computed several measures of association, including robust methods based on propensity scores (PSs) to control indication bias. Finally, we applied the Benjamini and Hochberg procedure of the false discovery rate (FDR). We applied this method in a multicenter retrospective cohort study using electronic medical records from 16 university hospitals of the Greater Paris area. We included all adult patients between 18 and 95 years old hospitalized in conventional wards for COVID-19 between February 1, 2020, and June 15, 2021. We investigated the association between drug prescription within 48 hours from admission and 28-day mortality. We validated our data-driven pipeline against a knowledge-based pipeline on 3 treatments of reference, for which experts agreed on the expected association with mortality. We then demonstrated its clinical relevance by screening all drugs prescribed in more than 100 patients to generate pharmacological hypotheses.
RESULTS: A total of 5783 patients were included in the analysis. The median age at admission was 69.2 (IQR 56.7-81.1) years, and 3390 (58.62%) of the patients were male. The performance of our automated pipeline was comparable or better for controlling bias than the knowledge-based adjustment set for 3 reference drugs: dexamethasone, phloroglucinol, and paracetamol. After correction for multiple testing, 4 drugs were associated with increased in-hospital mortality. Among these, diazepam and tramadol were the only ones not discarded by automated diagnostics, with adjusted odds ratios of 2.51 (95% CI 1.52-4.16, Q=.1) and 1.94 (95% CI 1.32-2.85, Q=.02), respectively.
CONCLUSIONS: Our innovative approach proved useful in generating pharmacological hypotheses in an outbreak setting, without requiring a priori knowledge of the disease. Our systematic analysis of early prescribed treatments from patients hospitalized for COVID-19 showed that diazepam and tramadol are associated with increased 28-day mortality. Whether these drugs could worsen COVID-19 needs to be further assessed.

The National Culture Collection of Pathogens (NCCP) is a microbial resource bank in Korea that collects pathogen resources causing infectious disease in human and distributes them for research and education. The NCCP bank attempts to discover strains with various characteristics and specific purposes to provide diverse resources to researchers. Staphylococcus aureus American Type Culture Collection (ATCC) 6538P is used as a reference strain in the microbial assay for antibiotics in the Korean and in the United States Pharmacopoeias. We aimed to analyze domestically isolated microbial resources from the NCCP to replace the S. aureus reference strain. Staphylococcus aureus strains were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the VITEK-2 system and characterized by multilocus sequence typing, 16S rRNA sequencing, and antibiotic susceptibility testing. Several candidate strains had similar characteristics as the reference strain. Among them, the nucleotide sequence of the 16S rRNA region of NCCP 16830 was 100% identical to that of the reference strain; it was sensitive to six types of antibiotics and showed results most similar to the reference strain. A validity evaluation was conducted using the cylinder-plate method. NCCP 16830 presented valid results and had the same performance as ATCC 6538P; therefore, it was selected as an alternative candidate strain.

Differences in gendered knowledge about plants are contingent on specific cultural domains. Yet the boundaries between these domains, for example food and medicine, are sometimes blurred, and it is unclear if and how gender plays a role in creating a continuum between them. Here, we present an in-depth evaluation of the links between gender, medicinal plant knowledge, and culinary culture in Marrakech, Morocco. We interviewed 30 women and 27 men with different socio-demographic characteristics and evaluated how gender and cooking frequency shape their food and medicinal plant knowledge. We documented 171 ethno-taxa used in Marrakshi households as food, medicine, or both, corresponding to 148 botanical taxa and three mixtures. While no clear differences appear in food plant knowledge by gender, women have a three-fold greater knowledge of medicinal plants, as well as plants with both uses as food and medicine. Women\'s medicinal and food plant knowledge increases with their reported frequency of cooking, whereas the opposite trend is observed among men. Men who cook more are often single, have university-level degrees, and may be isolated from the channels of knowledge transmission. This demonstrates that the profound relations between the culinary and health domains are mediated through gender.

Extemporaneous compounding takes place in community and hospital pharmacies. There are usually specialist compounding pharmacies in major towns and cities, but any pharmacy may undertake compounding as long as they have appropriate facilities according to state-based legislation (e.g. allocated clean bench, specific compounding equipment). Although development is a continuous process, companies are customizing features to meet the majority of patient needs, but the very nature of the process cannot meet all patient needs. The risk-benefit ratio of using traditionally compounded medicines is favorable for patients who require specialized medications that are not commercially available, as they would otherwise not have access to suitable treatment. However, if an FDA-approved drug is commercially available, the use of an unapproved compounded drug confers additional risk with no commensurate benefit. Published reports of independent testing by the FDA, state agencies, and others consistently show that compounded drugs fail to meet specifications at a considerably higher rate than FDA-approved drugs. Compounded sterile preparations pose the additional risk of microbial contamination to patients. In the last 11 years, three separate meningitis outbreaks have been traced to purportedly \'sterile\' steroid injections contaminated with fungus or bacteria, which were made by compounding pharmacies. The 2012 outbreak has resulted in intense scrutiny of pharmacy compounding practices and increased recognition of the need to ensure that compounding is limited to appropriate circumstances.

BACKGROUND: Assessing the effectiveness of in-service training courses in order to achieve the desired goals and reduce the waste of costs and opportunities in the system is necessary. The purpose of this study was to determine the effectiveness of the \"pharmacopeia home health\" course considering its importance in different aspects using the Kirkpatrick model.
METHODS: The present study was a quasi-experimental conducted at community health workers (CHWs) on three levels of reaction, learning, and behavior. In each phase, a valid questionnaire was used to measure the outcome according to the Ministry of Health guidelines with pretest and posttest measurements. The data were analyzed through SPSS 23, using descriptive statistics and repeated measures test and general linear model.
RESULTS: The results of the study showed that at the level of reaction in terms of content and holding, conditions of implementation were favorable. Findings at the level of learning showed that the training course was only effective in enhancing the knowledge and awareness about drug maintenance and had no significant effect on other areas. In the third level, the results of the CHWs\' performance showed that in some areas, the results were influenced by the demographic variables.
CONCLUSIONS: The present study showed the effectiveness of education in different areas using on the Kirkpatrick model. Given the lack of impact of education in some areas in the present study and on the other, it is necessary to consider cooperative learning methods in order to develop the effectiveness of the courses.

Background-Medicinal plants are traditionally used as infusions or decoctions for their antioxidant, anti-inflammatory, hypolipidemic and anti-diabetic properties. Purpose-The aim of the study was to define the polyphenol composition and to assess the antioxidant capacity of eight medicinal plants from Reunion Island referred to in the French Pharmacopeia, namely Aphloia theiformis, Ayapana triplinervis, Dodonaea viscosa, Hubertia ambavilla, Hypericum lanceolatum, Pelargonium x graveolens, Psiloxylon mauritianum and Syzygium cumini. Methods-Polyphenol content was assessed by biochemical assay and liquid chromatography coupled to mass spectrometry. Antioxidant capacity was assessed by measuring DPPH reduction and studying the protective effects of herbal preparation on red blood cells or preadipocytes exposed to oxidative stress. Results-Polyphenol content ranged from 25 to 143 mg gallic acid equivalent (GAE)/L for infusions and 35 to 205 mg GAE/L for decoctions. Liquid chromatography coupled to mass spectrometry analysis showed the presence of major bioactive polyphenols, such as quercetin, chlorogenic acid, procyanidin and mangiferin. Antioxidant capacity assessed by different tests, including DPPH and Human red blood cell (RBC) hemolysis of herbal preparations, demonstrated a dose-dependent effect whatever the extraction procedure. Our data suggest that decoction slightly improved polyphenol extraction as well as antioxidant capacity relative to the infusion mode of extraction (DPPH test). However, infusions displayed a better protective effect against oxidative stress-induced RBC hemolysis. Conclusion-Traditional preparations of medicinal plant aqueous extracts (infusions and decoctions) display antioxidant properties that limit oxidative stress in preadipocytes and red blood cells, supporting their use in the context of metabolic disease prevention and treatment.

This article presents the development of a reversed-phase ultra-high-performance liquid chromatographic method for determining process-related impurities in ropinirole hydrochloride drug substance applying the analytical quality by design approach. The current pharmacopeial method suffers from selectivity issues due to two coelutions of two pairs of impurities. The development of a new method began with preliminary experiments, based on which the Acquity UPLC BEH C8 was selected as the most appropriate column. The effects of six different critical method parameters (CMPs) were then investigated using a fractional factorial screening design. Column temperature, the ratio of methanol in mobile phase B, and gradient slope turned out to be highly significant CMPs in achieving critical resolutions, and they were further evaluated using a central composite face-centered response-surface design. Mathematical models were created by applying a multiple linear regression method. Based on the elution order of an unknown degradation impurity and impurity C, two design spaces were established, and for each design space an optimal combination of CMPs was determined. The method developed was validated for precision, accuracy, linearity, and sensitivity, and it was proven suitable for determining nine process-related impurities of ropinirole.

This article presents the development of a reversed-phase (RP) high-performance liquid chromatographic (HPLC) method for determination of process-related impurities in a celecoxib drug substance following Analytical Quality by Design (AQbD) principles. The method from European Pharmacopeia (EP) for celecoxib drug substance does not sufficiently separate celecoxib from its EP impurity B because the system suitability criterion is not achieved (resolution NLT 1.8). The same issue was observed with the proposed method from United States Pharmacopeia (USP) for celecoxib capsules, where EP impurity A elutes under the main peak. A new HPLC method was developed that eliminates the disadvantages of the two pharmacopeial methods and is capable of efficiently separating and determining all seven impurities listed in EP and the proposed USP monographs. The development of a new HPLC method started with method scouting, in which various C18 and phenyl stationary phases were tested. Improved selectivity was obtained only with a chiral stationary phase. An immobilized Chiralpak IA-3 column used in RP mode turned out to be the most appropriate for method optimization. The ratio of acetonitrile in the mobile phase, flow rate, and column temperature were recognized as critical method parameters (CMPs) and were further investigated using a central composite face response-surface design. A multiple linear regression (MLR) method was applied to fit the mathematical models on the experimental data to determine factor-response relationships. The models created show adequate fit and good prediction abilities. The Monte Carlo simulation method was used to establish the design space. The method developed was verified in terms of precision, sensitivity, accuracy, and linearity, and the results showed that the new method is suitable for determination of seven process-related impurities of celecoxib.