Search

In the past 50 years, Cannabis sativa (C. sativa) has gone from a substance essentially prohibited worldwide to one that is gaining acceptance both culturally and legally in many countries for medicinal and recreational use. As additional jurisdictions legalize Cannabis products and the variety and complexity of these products surpass the classical dried plant material, appropriate methods for measuring the biologically active constituents is paramount to ensure safety and regulatory compliance. While there are numerous active compounds in C. sativa the primary cannabinoids of regulatory and safety concern are (-)-Δ⁹-tetrahydrocannabinol (THC), cannabidiol (CBD), and their respective acidic forms THCA-A and CBDA. Using the US Food and Drug Administration (FDA) bioanalytical method validation guidelines we developed a sensitive, selective, and accurate method for the simultaneous analysis CBD, CBDA, THC, and THCA-A in oils and THC & CBD in more complex matrices. This HPLC-MS/MS method was simple and reliable using standard sample dilution and homogenization, an isocratic chromatographic separation, and a triple quadrupole mass spectrometer. The lower limit of quantification (LLOQ) for analytes was 0.195 ng/mL over a 0.195-50.0 ng/mL range of quantification with a coefficient of correlation of >0.99. Average intra-day and inter-day accuracies were 94.2-112.7% and 97.2-110.9%, respectively. This method was used to quantify CBD, CBDA, THC, and THCA-A in 40 commercial hemp products representing a variety of matrices including oils, plant materials, and creams/cosmetics. All products tested met the federal regulatory restrictions on THC content in Canada (1,000 (an oil-based product). Overall, the method proved amenable to the analysis of various commercial products including oils, creams, and plant material and may be diagnostically indicative of adulteration with non-hemp C. sativa, specialized hemp cultivars, or unique manufacturing methods.

SummaryThirty-one strains of mesophilic and thermophilic lactic acid bacteria and their respective phages were tested for their minimum, optimum and maximum multiplication temperatures. Culture growth was strongly influenced by temperature during the first few hours of incubation, but less so after 24 h. Most of the phages showed the same pattern of development as their hosts, but one phage lysing a thermophilic lactobacillus and 3 phages lysing mesophilic streptococci proved temperature-sensitive, having a lower maximum temperature than that of their hosts. One phage was unusual in that its minimum development temperature was 7 °C above that of its host. Differences in temperature sensitivity were insufficient to reduce risk of phage infection by temperature control in industrial processes.

The natural alkaloid berberine has been ascribed numerous health benefits including lipid and cholesterol reduction and improved insulin sensitivity in diabetics. However, oral (PO) administration of berberine is hindered by poor bioavailability and increasing dose often elicits gastro-intestinal side effects. To overcome the caveats associated with oral berberine, we developed transdermal (TD) formulations of berberine (BBR) and the berberine precursor dihydroberberine (DHB). These formulations were compared to oral BBR using pharmacokinetics, metabolism, and general safety studies in vivo. To complete this work, a sensitive quantitative LC-MS/MS method was developed and validated according the FDA guidelines for bioanalytical methods to simultaneously measure berberine, simvastatin, and simvastatin hydroxy acid with relative quantification used for the berberine metabolite demethylene berberine glucuronide (DBG). Acute pharmacokinetics in Sprague-Dawley rats demonstrated a statistically relevant ranking for berberine bioavailability based upon AUC0-8 as DHB TD > BBR TD >> BBR PO with similar ranking for the metabolite DBG, indicating that transdermal administration achieves BBR levels well above oral administration. Similarly, chronic administration (14 days) resulted in significantly higher levels of circulating BBR and DBG in DHB TD treated animals. Chronically treated rats were given a single dose of simvastatin with no observed change in the drugs bioavailability compared with control, suggesting the increased presence of BBR had no effect on simvastatin metabolism. This observation was further supported by consistent CYP3A4 expression across all treatment groups. Moreover, no changes in kidney and liver biomarkers, including alanine aminotransferase and alkaline phosphatase, were observed between treatment formats, and confirming previous reports that BBR has no effect on HMG-CoA expression. This study supports the safe use of transdermal compositions that improve on the poor bioavailability of oral berberine and have the potential to be more efficacious in the treatment of dyslipidemia or hypercholesterolemia.

Resume ľaction antimicrobienne de Remanex Zyma et de ses constituants (borate de phenyl-mercure et hexachlorophene) a ete experimentee sur des spores ?une souche de Strepto-myces sp., isolee des eaux du lac Leman (Suisse), soit: a) les spores de la souche sauvage; b) les spores ?une subculture preparee a partir ?un individu de la souche initiale qui a survecu a 2 min ?UV germicides; c) dito, mais 10 min ?UV germicides. Dans tous les cas, les resultats montrent que Remanex possede une efficacite nettement plus forte que ses principes actifs isoless ou associes, mais sans excipient. ?autre part, les spores qui ont survecu a la plus forte dose ?UV administree ont fourni une subculture dont la resistance aux traitements desinfectants decrits dans ce travail s'est revelee superieure a. celle de la souche non ou faiblement irradiee. Zusammenfassung Die antibakterielle Wirkung von Remanex Zyma und seinen Bestandteilen (Phenyl-quecksilberborat und Hexachlorophen) wurde an Sporen eines aus dem Genfer See (Schweiz) isolierten Stammes Streptomyces sp. untersucht, und zwar an: a) Sporen des wilden Stammes; b) Sporen der Subkultur eines Keims der Primarkultur, der eine 2 min lange keimtotende UV-Bestrahlung uberlebte; c) Sporen der Subkultur eines Keims der Primarkultur, der eine 10 min lange keim-totende UV-Bestrahlung uberlebte. Remanex erwies sidi in alien Fallen als weitaus wirksamer als seine einzeln oder assoziiert ohne Excipiens vorliegenden aktiven Wirkstoffe. Diejenigen Sporen, die die hochstdosierte UV-Bestrahlung uberlebten, entwickelten Kolonien, deren Resistenz gegenuber den in dieser Arbeit beschriebenen Desinfizienzien groser als diejenige der nicht oder schwach bestrahlten Kulturen war. Summary The antimicrobial activity of Remanex Zyma and its components (phenymercuric borate and hexachlorophene) was tested on the spores of a strain of Streptomyces sp., isolated from the waters of the lake of Geneva (Switzerland), namely: a) the spores of the wild strain; b) the spores of a subculture prepared from a component of the original strain which survived 2 min of germicidal UV irradiation; c) ditto, but with 10 min of germicidal UV irradiation. Remanex was shown in all cases to have a definitely more powerful action than either of its components alone or in combination without excipient. The spores which survived the higher dose of irradiation formed a subculture with a higher resistance to the Desinfectants described in this study than the non- or weakly-irradiated strain.