Drug Metabolism and Bioanalysis Letters - Volume 17, Issue 2, 2024

Lobeglitazone sulfate is a novel thiazolidinedione drug used for the therapy of type 2 diabetes. Recent pre-clinical studies show that the drug is also effective in attenuating mucus hypersecretion and airway inflammation caused due to ovalbumin-induced asthma.

This study aimed to develop an accurate, simple, and cost-effective analytical method for the quantification of lobeglitazone sulfate in bulk and pharmaceutical dosage forms by UV spectrophotometric technique.

The drug was identified by FTIR (ATR) instrument and the method development was performed with methanol as the solvent. In compliance with the ICH Q2(R2) guidelines, all the important validation parameters, such as linearity, accuracy, Limit of Detection (LOD), precision, specificity, Limit of Quantification (LOQ), and robustness were determined.

The maximum absorption wavelength of lobeglitazone sulfate was found to be 248 nm. The linearity range was established from 2-14 μg/mL with a linearity equation of y = 0.0361x + 0.0024 and r² = 0.9987. The accuracy of the analytical method was found to be in the range of 99.37-100.41%. The precision studies were performed under three subsets of repeatability, intra-day, and inter-day, and the results recorded were within the acceptance limits, i.e., %RSD (<2%). The developed analytical method's Limit of Detection (LOD) and Limit of Quantification (LOQ) values were 0.07 μg/mL and 0.22 μg/mL, respectively.

The developed analytical method has been found to be valuable in regular quality control analysis of lobeglitazone sulfate in pharmaceutical industries. The adopted approach of the developed method has been found to be facile, accurate, precise, and economical.

This study developed a UV spectrophotometric method for quantifying allopurinol and lycopene in both bulk and dosage forms, aiming for simplicity and practicality.

The method was developed and validated using methanol and lycopene in phosphate buffer saline at various pH levels (7.4, 6.8, 1.2, 5.5). Validation parameters included linearity, accuracy, precision, limit of quantification (LOQ), and limit of detection (LOD) according to ICH standards.

The method demonstrated high sensitivity and linearity over a concentration range of 4-20 µg/ml, adhering to Beer's law. The LOQ and LOD were 2-18 µg/ml and 2-6 µg/ml, respectively. Optimal absorbance wavelengths were 251 nm for lycopene and 471 nm for allopurinol. Calibration curves showed a high correlation coefficient (0.9994), indicating a strong linear relationship.

The developed UV spectrophotometric method is effective, interference-free, and suitable for routine quality control, providing reliable measurements for allopurinol and lycopene.

One of the world's most serious health issues is arsenic toxicity. Prolonged consumption of Arsenic contaminated water causes cognitive damage in the developing and adult brain. The present research investigated how sodium arsenite-induced neurotoxicity in SD rats was affected by rolipram, a PDE4 inhibitor, and vinpocetine, a PDE1 inhibitor.

The arsenic concentration was determined, which indicates the accumulation of arsenic in blood. The low weight of the brain indicates the adverse effects on the brain, which was significantly improved by rolipram and vinpocetine. Biochemical markers (MDA, GSH, CAT, and SOD) and protein expression of CREB and P-CREB were studied in the hippocampal region of the brain.

The reduced antioxidant activity and elevated levels of inflammation were significantly improved by rolipram and vinpocetine administration. Additionally, rolipram and vinpocetine significantly increased the CREB and P-CREB expression in the hippocampi of rat brains.

PDE4 and PDE1 inhibition in arsenic-induced neurotoxicity could be a novel approach and a new drug therapy for arsenic-induced neurotoxicity.

Efinaconazole is a topical antifungal medication that is effective against fungal infections of the toenails. In addition, due to its application on the skin, minimal systemic absorption takes place on the epidermic layer, which leads to the availability of lower-level concentration in the bloodstream. Although several reported methods in the literature describe the quantification of Efinaconazole using conventional techniques like HPTLC and HPLC, these methods lack the necessary sensitivity and selectivity to be directly applied for quantification in biological samples.

Current research work aimed to develop a rapid, specific, selective, and sensitive method using plasma as one of the biological samples for quantification of Efinaconazole (EZ) in the presence of Fluconazole (FZ) as an internal standard by tandem mass spectrometry (LC-MS/MS).

Chromatographic separation was achieved with a Thermo Hypersil Gold (100 mm x 2.1 mm, 1.9 µm) UPLC column using a mobile phase composed of 20% formic acid-water (0.1%) and 80% methanol. Liquid-liquid extraction (LLE) was employed for sample preparation. Efinaconazole and the internal standard were detected using the heated electrospray ionization (HESI) technique in parallel reaction monitoring (PRM) mode.

The developed method displayed a linearity range of 1 to 2000 pg/mL (0.001-2 ng/mL). Precision and accuracy for the lower limit of quantitation, low, mid, and high-quality control (QC) levels demonstrated a variance of less than 5% and an accuracy of 99 to 103%. Long-term stability was confirmed under various conditions, including storage in an auto-sampler, at room temperature, in a deep freezer, and after freeze-thaw cycles.

The validated LC-MS/MS method has exceptional sensitivity, specificity, selectivity, rapid analysis, minimal requirement of sample quantity, wide dynamic range of concentration, robustness, and reproducibility, making it an indispensable tool, especially in fields of in vitro Permeation Testing (IVPT), in vitro Release Testing (IVRT), Pharmacokinetic, Toxicology, Clinical studies, and in drug development program for the quantification of Efinaconazole.

The current study focused on formulating ocular films embedded with levofloxacin for the treatment of conjunctivitis by employing the solvent-casting technique.

These films were formulated with gelatin, Aloe barbadensis leaves mucilage (ABLM), and HPMC K4M to enhance the therapeutic effectiveness of levofloxacin. Various evaluations were carried out to confirm the quality and stability of the films, including assessments of thickness, weight uniformity, uniformity in LFX, % loss of moisture, and permeation. In vitro drug release studies were conducted to simulate ocular environments and analyze the precise release of LFX.

The films exhibited uniform thickness (0.15–0.19 mm) and weight (61.85–65.54 mg) with a consistent film area (0.502 cm²). LFX content ranged from 85.66% to 97.03%, with T-6 being the most uniform. Moisture loss was found to be 7.98–9.55%, and absorption (highest in T-6, i.e., 18.05%) increased with gelatin. LFX permeation peaked at 97.03% (T-6) in 24-h diffusion studies. T-8 demonstrated exceptional mucoadhesion (>10 h), and ANOVA confirmed the important influence of gelatin, ABLM, and HPMC K4M on LFX content (F-value: 129.91, p=0.0010).

The study concluded that combining ABLM with HPMC K4M enabled consistent, diffusion-controlled release of LFX, offering an effective and sustained formulation for treating conjunctivitis.