Development and validation of an LC–MS/MS method for quantification of NC-8 in rat plasma and its application to pharmacokinetic studies

ent-16-Oxobeyeran-19-N-methylureido (NC-8) is a recently synthesized derivative of isosteviol that showed anti-hepatitis B virus (HBV) activity by disturbing replication and gene expression of the HBV and by inhibiting the host toll-like receptor 2/nuclear factor-κB signaling pathway. To study its pharmacokinetics as a part of the drug development process, a highly sensitive, rapid, and reliable liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed and validated for determining NC-8 in rat plasma. After protein precipitation extraction, the chromatographic separation of the analyte and internal standard (IS; diclofenac sodium) was performed on a reverse-phase Luna C18 column coupled with a Quattro Ultima triple quadruple mass spectrometer in the multiple-reaction monitoring mode using the transitions, m/z 347.31 → 75.09 for NC-8 and m/z 295.89 → 214.06 for the IS. The lower limit of quantitation was 0.5 ng/mL. The linear scope of the standard curve was between 0.5 and 500 ng/mL. Both the precision (coefficient of variation; %) and accuracy (relative error; %) were within acceptable criteria of <15%. Recoveries ranged from 104% to 113.4%, and the matrix effects (absolute) were non-significant (CV ≤ 6%). The validated method was successfully applied to investigate the pharmacokinetics of NC-8 in male Sprague–Dawley rats. The present methodology provides an analytical means to better understand the preliminary pharmacokinetics of NC-8 for investigations on further drug development

Estimation of Pediatric Dosage of Antimalarial Drugs, Using Pharmacokinetic and Physiological Approach

Most of the individuals who die of malaria in sub–Saharan Africa are children. It is, therefore, important for this age group to have access to the right treatment and correct dose. Artemether—lumefantrine is one of the fixed dose combination therapies that was approved by the World Health Organization to treat malaria. However, the current recommended dose has been reported to cause underexposure or overexposure in some children. The aim of this article was, therefore, to estimate the doses that can mimic adult exposure. The availability of more and reliable pharmacokinetic data is essential to accurately estimate appropriate dosage regimens. The doses in this study were estimated using the physiological information from children and some pharmacokinetic data from adults due to the lack of pediatric pharmacokinetic data in the literature. Depending on the approach that was used to calculate the dose, the results showed that some children were underexposed, and others were overexposed. This can lead to treatment failure, toxicity, and even death. Therefore, when designing a dosage regimen, it is important to know and include the distinctions in physiology at various phases of development that influence the pharmacokinetics of various drugs in order to estimate the dose in young children. The physiology at each time point during the growth of a child may influence how the drug is absorbed, gets distributed, metabolized, and eliminated. From the results, there is a very clear need to conduct a clinical study to further verify if the suggested (i.e., 0.34 mg/kg for artemether and 6 mg/kg for lumefantrine) doses could be clinically efficacious

A Malawian pharmaceutical response to the COVID-19 Pandemic

The COVID-19 pandemic has elicited swift and innovative responses due to the severity of the outbreak. Higher education institutions worldwide with pharmacy programs have identified vital gaps in COVID-19 care and has undertaken proactive steps to aid in the fight against the coronavirus. In Malawi, the Kamuzu University of Health Science’s Department of Pharmacy initiated the production of a modified formulation of the World Health Organization’s (WHO) recommended hand sanitizer. This manufacturing venture involved mobilizing the pharmacy faculty, identifying gaps in supplies and equipment, and utilizing evidenced-based information to create a high-quality sanitation product, which passed the requirements as tested by the Malawi Bureau of Standards. The department of pharmacy is expanding their distribution of the product to meet the needs of frontline healthcare workers and vulnerable populations. With historical issues of accessing care in Malawi and with COVID-19’s spread among healthcare workers, this hand sanitizer venture is vital in the public healthcare’s system response. The department of pharmacy will continue to lead the pharmacy profession in Malawi to provide targeted interventions in this unprecedented time