Drug Metabolism and Bioanalysis - Online First

Detecting toxicity patterns in metabolic changes is a key indicator of potential threats. Metabolomics may provide an alternative way to find biomarkers for drug overdose and toxicity. In an acetaminophen overdose, glutathione scavenging causes mitochondrial malfunction and hepatocyte death. Metabolomics methods have enabled the discovery of novel mechanisms of liver injury in acetaminophen (APAP) overdose.

We conducted a peer-reviewed scientific review to assess the studies on the application of metabolomics in APAP poisoning. We searched PubMed and Scopus databases until February 28, 2025, for relevant original articles. We also looked into the clinicaltrials.gov website and the Indian clinical trial registry.

Our initial search yielded 302 articles, after duplicates and initial screening. Two hundred and nine (209) articles underwent full-text review. Of these, 191 articles were excluded, and 18 studies were included. There were 1503 subjects, and 24 metabolomics techniques were used. Seven trials were registered in clinicaltrials.gov, and none were registered in the CTRI.

Metabolic intermediates are more likely to pass through intact cell membranes and be detected in blood before cell death. Thus, metabolomics could be a potential strategy to identify damage biomarkers relevant at earlier periods.

APAP can be considered a multifunctional drug with significantly fewer adverse effects; however, it still affects the liver when used chronically. Scientists continue to push the boundaries of data extraction, and it is widely acknowledged that a lack of tools for data integration hampers the full manifestation of metabolomics technologies. This research increases our understanding of metabolomics use in APAP-induced liver injury.

Drug-drug interactions between statins and azole antifungal agents, due to the inhibition of the CYP3A4 enzyme by antifungals, increase the risk of adverse effects from statins. Thus, a precise bioanalytical method for quantifying Itraconazole and Atorvastatin in human plasma is essential.

A liquid chromatographic method with protein precipitation and liquid-liquid extraction was developed. Rosuvastatin calcium served as the internal standard. The method was validated per ICH M10 and USFDA guidelines and used to analyze spiked plasma samples.

The method effectively separated Itraconazole, Atorvastatin, and the internal standard without plasma interference. It achieved linear responses for each drug in the 0.1-3.0 μg/mL range with regression coefficients > 0.99. The RSD for within-run and between-run responses was < 5%, and the average recovery exceeded 64%.

The method accurately and precisely measured each analyte at the LLOQ level (0.1 μg/mL). A sensitive and selective bioanalytical HPLC method was developed, validated, and applied for the simultaneous estimation of Itraconazole and Atorvastatin in human plasma.

This method ensures safe and effective co-administration of these medications in clinical practice, benefiting patient care.

Hypertension is one of the most common non-communicable diseases, and reports indicate that its prevalence is escalating globally due to several factors. Studies in different countries have shown an upsurge in the use of Herbal Medicinal Products (HMPs), including herbal antihypertensive medicines taken by people with hypertension, and 20-80% of hypertensive patients concurrently use these herbal medicines and conventional antihypertensive medicines or other drugs. The safety and efficacy of the concurrent use of herbal and orthodox medicines are of great concern because of the high possibility of herb-drug interactions.

An extensive literature search was undertaken, and the information obtained was subjected to critical analysis. This review aimed to update the available data on HMPs with reproducible evidence-based antihypertensive efficacies. Additionally, the major phytochemical and bioactive constituents of these HMPs were identified along with a discussion of their potential to modulate activities of drug-metabolizing enzymes and drug transport systems, especially P-glycoprotein.

More than 50 commonly used medicinal plants from different regions of the world have been documented for their anti-hypertensive activity. Most of these studies used animal models to authenticate the antihypertensive activities of the herbs. In contrast, a few studies on extracts of Hibiscus sabdariffa, Allium sativum, Apium graveolens, Nigella sativa, Linum usitatissimum, and Camellia sinensis involved clinical trials. Potentials for herb-drug interactions varied among the clinically effective HMPs due to the wide variability in their phytochemical constituents.

Safety issues in using these HMPs were highlighted by the identification of beneficial or adverse, clinically significant herb-drug interactions.

The antifungal drug bifonazole, a substituted imidazole, exhibits broad-spectrum in vitro action against Gram-positive bacteria, yeasts, moulds, dermatophytes, and dimorphic fungi.

The analysis was carried out using a C18 reversed-phase column (250 mm × 4.6 mm, 5 μm particle size) maintained at a constant temperature of 25°C. Methanol and 0.1% trifluoroacetic acid were utilized as the mobile phase. Detection was performed at 256 nm with a UV detector, and quantification was achieved using the standard method. The method validation was carried out for various parameters as per ICH guidelines. The developed eco-friendly HPLC method was employed to assess the vesicle size and entrapment efficiency of the transethosomes. The greenness assessment tool was applied to assess the environmental sustainability of the proposed HPLC method.

The retention time was under 5 minutes, confirming the method's appropriateness for routine analysis. Linearity was observed in the concentration range of 5 to 25µg/ml, LOD and LOD were 2µg/ml and 8µg/ml respectively. Intraday and interday precision were within ICH limits (<2). The method was successfully used to analyse vesicle size (178nm) and entrapment efficiency (77.6±0.72%.) of the nanoformulation. The greenness assessment tool yielded a value of 0.71.

The developed method is both analytically sound and eco-friendly, making a significant improvement in the estimation of bifonazole. The developed method's LOD and LOQ values were sufficiently low to facilitate the detection and measurement of bifonazole in pharmaceutical formulations frequently utilized in research applications, thereby supporting its potential utility in analytical and research settings.

Overall, this green, eco-friendly HPLC method is well-suited for routine analysis of bifonazole, demonstrating excellent cost-effectiveness, sensitivity, precision, and robustness.