Search

Metabolic stability of a compound is an important factor to be considered during the early stages of drug discovery. If the compound has poor metabolic stability, it never becomes a drug even though it has promising pharmacological characteristics. For example, a drug is quickly metabolized in the body; it does not have sufficient in vivo exposure levels and leads to the production of toxic, non-active or active metabolites. A drug is slowly metabolized in the body it could remain longer periods in the body and lead to unwanted adverse reactions, toxicity or may cause drug interactions. Metabolic stability assay is performed to understand the susceptibility of the compound to undergo biotransformation in the body. Intrinsic clearance of the compound is measured by metabolic stability assays. Different in vitro test systems including liver microsomes, hepatocytes, S9 fractions, cytosol, recombinant expressed enzymes, and cell lines are used to investigate the metabolic stability of drugs. Metabolite profiling is a vital part of the drug discovery process and LC–MS plays a vital role. The development of high-resolution (HR) MS technologies with improved mass accuracy, in conjunction with novel data processing techniques, has significantly improved the metabolite detection and identification process. HR-MS based data acquisition (ion intensity-dependent acquisition, accurate-mass inclusion list-dependent acquisition, isotope pattern-dependent acquisition, pseudo neutral loss-dependent acquisition, and mass defect-dependent acquisition) and data mining techniques (extracted ion chromatogram, product ion filter, mass defect filter, isotope pattern filter, neutral loss filter, background subtraction, and control sample comparison) facilitate the drug metabolite identification process.

Metabolic stability of a compound is an important factor to be considered during the early stages of drug discovery. If the compound has poor metabolic stability, it never becomes a drug even though it has promising pharmacological characteristics. For example, a drug is quickly metabolized in the body; it does not have sufficient in vivo exposure levels and leads to the production of toxic, non-active or active metabolites. A drug is slowly metabolized in the body it could remain longer periods in the body and lead to unwanted adverse reactions, toxicity or may cause drug interactions. Metabolic stability assay is performed to understand the susceptibility of the compound to undergo biotransformation in the body. Intrinsic clearance of the compound is measured by metabolic stability assays. Different in vitro test systems including liver microsomes, hepatocytes, S9 fractions, cytosol, recombinant expressed enzymes, and cell lines are used to investigate the metabolic stability of drugs. Metabolite profiling is a vital part of the drug discovery process and LC–MS plays a vital role. The development of high-resolution (HR) MS technologies with improved mass accuracy, in conjunction with novel data processing techniques, has significantly improved the metabolite detection and identification process. HR-MS based data acquisition (ion intensity-dependent acquisition, accurate-mass inclusion list-dependent acquisition, isotope pattern-dependent acquisition, pseudo neutral loss-dependent acquisition, and mass defect-dependent acquisition) and data mining techniques (extracted ion chromatogram, product ion filter, mass defect filter, isotope pattern filter, neutral loss filter, background subtraction, and control sample comparison) facilitate the drug metabolite identification process.

Summary Objectives The objective of this study is to investigate the effect of surfactants (polysorbate 80 and sodium lauryl sulphate) and hydrophilic polymers (polyvinylpyrrolidone and polyethylene glycol 6000) on the stability of candesartan cilexetil under isothermal stress conditions (100°C, 48 h). Methods HPLC method was employed to evaluate the drug content and formation of degradation products in stress samples. Drug and degradation products were separated on Hypersil BDS C18 (250 × 4.6 mm, 5 μ) column using acetonitrile-water (pH 2.8) in the ratio of 85:15% v/v as a mobile phase. Result Similar degradation behaviour of drug was observed with polyvinylpyrrolidone, polyethylene glycol 6000 and polysorbate 80; four common degradation peaks were observed at the retention time of 3.7, 4.5, 7.8 and 11 minutes. One extra common degradation peak of very low intensity was also observed with polyethylene glycol 6000 and polysorbate 80 at the retention time of 4.2 min. The drug was eluting at the retention time of 5.4 min. In the case of sodium lauryl sulphate, two prominent degradation peaks were observed at the retention time of 3.7 and 13.25 min along with few very low-intensity degradation peaks. Conclusion The drug showed 41%, 64%, 72% and 98% degradation in presence of polyvinylpyrrolidone, polyethylene glycol 6000, polysorbate 80 and sodium lauryl sulphate, respectively.

The equilibrium dissociation constant (KD) is the basic parameter to evaluate the binding property of the chemical structure of compounds. Thus, a variety of analytical methods have been established to determine the KD values, including radioligand binding assay, surface plasmon resonance method, fluorescence energy resonance transfer method, affinity chromatography, and isothermal titration calorimetry. Here we present a detailed overview of the dissociation equilibria of Eberconazole nitrate (EBZ) in homogeneous and heterogeneous systems, focusing primarily on methods that are based on spectrophotometrically of the dissociation reaction. The Dissociation equilibria of Eberconazole nitrate (EBZ) in homogeneous and heterogeneous systems were studied spectrophotometrically in Britton-Robinson’s (BR) buffer at 25°C. Acidity constant of EBZ in BR buffer was found to be 9.5. The effect of anionic, cationic and non-ionic surfactants applied in the concentration exceeding critical micellar concentration (cmc) on acid – base properties of EBZ were also examined. The results revealed a shift of pKa values in micellar media comparing to the values obtained in BR buffer. These shifts in pKa values are more in cationic and anionic micellar media compared with that of non-ionic. The observed differences in pKa values between micellar media and BR buffer solution ranged between -6.0 to -2.0 units. The micellar-mediated pKa shifts can be attributed to the differences between the mean intrinsic solvent properties of the interfacial and bulk phases, with an additional contribution from the electrostatic micellar surface potential in the case of the charged aqueous micellar solutions.

A simple and cost effective spectrophotometric method is described for the determination of torsemide in pure form and in pharmaceutical formulations. The method is based on the formation of blue colored chromogen when the drug reacts with Folin-Ciocalteu (F-C) reagent in alkaline medium. The colored species has an absorption maximum at 760 nm and obeys beer's law in the concentration range 30 – 150 ug mL−1. The absorbance was found to increase linearly with increasing concentration of TSM, which is corroborated by the calculated correlation coefficient value of 0.9999 (n=8). The apparent molar absorptivity and sandell sensitivity were 1.896×103L mol−1cm−1and 0.183 μg cm−2, respectively. The slope and intercept of the equation of the regression line are 5.4x10−3and 1.00×10−4respectively. The limit of detection was 0.94.The optimum experimental parameters for the reaction have been studied. The validity of the described procedure was assessed. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The proposed method was successfully applied to the determination of TSM in pharmaceutical formulations.