New Analytical Method for the Determination of Metronidazole in Human Plasma: Application to Bioequivalence Study

Purpose: To develop new sensitive, accurate, rapid and reproducible high performance liquid chromatography (HPLC) method to determine  metronidazole levels in human plasma and to apply the method in a bioequivalence study.Methods: Metronidazole was extracted from human plasma through one step of protein precipitation by methanol using carbamazepine as internal standard (IS). After centrifugation of the plasma sample, the supernatant layer was separated and injected into HPLC system using Eclipse XDB-phenyl column. The mobile phase consisted of phosphate buffer (pH 4.5): acetonitrile (95:5, v/v). The UV detector was set at 320 nm. The bioavailability of the test metronidazole product (Brand A) was compared to a commercial metronidazole brand as reference product in 24 healthy volunteers who received a single dose equivalent to 500 mg of the test and reference products in a randomized balanced two-way cross-overdesign separated by two-week wash-out period.Results: Mean standard calibration curves of metronidazole over the concentration range of 0.05 . 30 ƒÊg/ml were linear. No significant differences were found based on analysis of variance of the pharmacokinetics parameters required for the assessment of bioequivalence of test and reference formulations. The mean value and 90 %CI of test/reference ratios for the derived parameters were: Cmax, 9.64 vs. 8.38 (0.93 . 1.10), AUC0-24, 124.6 vs.122.3 ƒÊg.h/mL (0.973 . 1.051) and AUC0-‡, 140.9 vs. 128.4 h/mL (1.15 . 1.23).Conclusion: The test metronidazole product was bioequivalent to the reference. The method is suitable for bioequivalence and pharmacokinetic studies in humans with a low limit of quantification of 0.05 ƒÊg/ml.Keywords: Metronidazole, Bioequivalence, HPLC, Pharmacokinetics, Human plasm

Green Hydrogen Recovery from Natural Gas Grids by Vacuum Pressure Swing Adsorption

This study focuses on the development of a conceptual vacuum pressure swing adsorption process (VPSA) for green hydrogen (GH) recovery from natural gas grids (NGGs). Accordingly, the kinetics-based separation of H-2 from NGG was achieved by using a commercial carbon molecular sieve (CMS-3K-172) adsorbent. To develop the VPSA cycle, the CMS-3K-172 was characterized, single- and multicomponent breakthrough curves for H-2 and CH4 were performed, and adsorption isotherms were collected between 195 and 273 K and pressures up to 18 bar. To separate H-2 (20%) from CH4 (80%), three different VPSA cycle configurations were designed and simulated by using Aspen Adsorption. The operational variables, such as step times, intermediate-to-high-pressure ratio, purge-to-feed ratio, and H-2 initial concentration, were evaluated for maximum values of purity, recovery, and adsorbent productivity. The results show that the VPSA processes can enrich H-2 in the product stream by up to 68% with a recovery of 92%.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support: (1) under project PTDC/EQU-EPQ/0467/2020 (DOI: 10.54499/PTDC/EQU-EPQ/0467/2020), (2) through the national funds FCT/MCTES (PIDDAC), CIMO UIDB/00690/2020 (DOI: 10.54499/UIDB/00690/2020) and UIDP/00690/2020 (DOI: 10.54499/UIDP/00690/2020); and SusTEC, LA/P/0007/2020 (DOI: 10.54499/LA/P/0007/2020), (3) by the national funds through FCT/MCTES (PIDDAC): LSRE-LCM, UIDB/50020/2020 (DOI: 10.54499/UIDB/50020/2020) and UIDP/50020/2020 (DOI: 10.54499/UIDP/50020/2020), and ALiCE, LA/P/0045/2020 (DOI: 10.54499/LA/P/0045/2020). Additionally, the authors thank the national funding by FCT, Foundation for Science and Technology, through the individual research grant SFRH/BD/7925/2020 of L.F.A.S.Z. Moreover, the authors are grateful to Osaka Co. for kindly providing the CMS-3K-172 studied in this work.info:eu-repo/semantics/publishedVersio

Quick and robust method for trace determination of MeHg in rice and rice products without derivatisation

Peer reviewedPostprin

Separation of CO2/N2 in Ion-Exchange binder-free beads of zeolite NaY for Post-Combustion CO2 capture

Ion-exchange on bare commercial zeolites can offer improved adsorption processes. In the context of CO2/N2 separation for post-combustion CO2 capture (PCC), here, we report, the effect of ion-exchange on commercial binder-free NaY zeolite with alkali (K+) and alkaline earth (Ca2+) metal cations, achieving exchange levels of 23 %, 58 %, and 95 % for K+ and 56 % and 71 % for Ca2+. Adsorption isotherms of CO2 and N2 were measured over a temperature range of 306–344 K and pressures up to 350 kPa. At low pressures, the CO2 adsorption capacity increases as Na+ ions are exchanged to a higher level of K+, while a reverse trend is observed for Ca2+ exchange. At 25 kPa and 306 K, the CO2 loading (mol∙kg−1) follows the order 2.01-Ca(71)Y < 2.63-Ca(56)Y < 4.05-NaY < 4.29-K(23)Y < 4.59-K(58)Y < 4.72-K(95)Y. The selectivities of CO2 (15 %)/N2 (85 %) at 306 K and 101.3 kPa range from 52 for Ca(71)Y to 101 for K(23)Y, compared to 89 in the bare NaY zeolite. The working capacities for the most promising exchanged sample (K(23)Y) exhibit superior values of 4.51, 2.98, and 2.41 mol∙kg−1 considering regeneration pressures of 3, 10, and 15 kPa, relative to a feed pressure of 101.3 kPa, respectively. Dynamic simulations were conducted using the Aspen Adsorption package to accurately predict both single- and binary-component breakthrough curves.This work was supported by national funds through FCT/MCTES (PIDDAC): (1) project PTDC/EQU-EPQ/0467/2020 (DOI:10.54499/ PTDC/EQU-EPQ/0467/2020); (2) CIMO, UIDB/00690/2020 (DOI: 10.54499/UIDB/00690/2020) and SusTEC, LA/P/0007/2020 (DOI: 10.54499/LA/P/0007/2020); (3) CICECO -Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020 & LA/P/0006/2020.info:eu-repo/semantics/publishedVersio

Protective Effect of Chemically Characterized Polyphenol-Rich Fraction from Apteranthes europaea (Guss.) Murb. subsp. maroccana (Hook.f.) Plowes on Carbon Tetrachloride-Induced Liver Injury in Mice

Apteranthes europaea (Guss.) Murb. subsp. maroccana (Hook.f.) Plowes (A. europaea) is a medicinal plant widely used in traditional medicines to treat various diseases including hepatic pathogenesis. This study was conducted to evaluate the protective effect of chemically characterized polyphenol-rich fraction from A. europaea on carbon tetrachloride-induced liver injury in mice. The chemical characterization of A. europaea polyphenol-rich fraction was carried out using HPLC-DAD (high-performance liquid chromatography (HPLC) with a diode-array detector (DAD)). Carbon tetrachloride (CCl4) was used to induce liver injuries in mice as described in previous works. A polyphenol-rich fraction from A. europaea was used at a dose of 50 mg/Kg to study its hepatoprotective effect. Next, histopathological and biochemical alterations were investigated. The HPLC analysis revealed the presence of several phenolic compounds: gallic acid, methyl gallate, rutin, ferulic acid, and resorcinol. Regarding the mice treated with a polyphenol-rich fraction from A. europaea up to 50 mg/Kg and carbon tetrachloride, no significant biochemical nor histological alterations occurred in their liver; meanwhile, serious biochemical and histopathological changes were noted for liver recovered from the mice treated with carbon tetrachloride only. In conclusion, A. europaea extract is a promising source of hepatoprotective agents against toxic liver injury

Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment

Variation in the human genome is a most important cause of variable response to drugs and other xenobiotics. Susceptibility to almost all diseases is determined to some extent by genetic variation. Driven by the advances in molecular biology, pharmacogenetics has evolved within the past 40 years from a niche discipline to a major driving force of clinical pharmacology, and it is currently one of the most actively pursued disciplines in applied biomedical research in general. Nowadays we can assess more than 1,000,000 polymorphisms or the expression of more than 25,000 genes in each participant of a clinical study – at affordable costs. This has not yet significantly changed common therapeutic practices, but a number of physicians are starting to consider polymorphisms, such as those in CYP2C9, CYP2C19, CYP2D6, TPMT and VKORC1, in daily medical practice. More obviously, pharmacogenetics has changed the practices and requirements in preclinical and clinical drug research; large clinical trials without a pharmacogenomic add-on appear to have become the minority. This review is about how the discipline of pharmacogenetics has evolved from the analysis of single proteins to current approaches involving the broad analyses of the entire genome and of all mRNA species or all metabolites and other approaches aimed at trying to understand the entire biological system. Pharmacogenetics and genomics are becoming substantially integrated fields of the profession of clinical pharmacology, and education in the relevant methods, knowledge and concepts form an indispensable part of the clinical pharmacology curriculum and the professional life of pharmacologists from early drug discovery to pharmacovigilance