Regulatory Updates and Analytical Methodologies for Nitrosamine Impurities Detection in Sartans, Ranitidine, Nizatidine, and Metformin along with Sample Preparation Techniques.

Nitrosamine impurities have been detected in various pharmaceutical products in recent days. Various sartans, ranitidine, nizatidine, and metformin have been recalled from the markets due to the high limit of nitrosamine impurities. This review aims to provide a brief overview of nitrosamine impurities, detection methods in detail, mechanism of action of nitrosamine impurities, sample preparation techniques, and regulatory limits. Numerous reported nitrosamine impurities also have been discussed with chemical structure. Various detection methods including LC-MS/MS, GC-MS-HS, and HPLC for nitrosamine impurities along with sartans, ranitidine, nizatidine, and metformin are being discussed in this review article. Various sample preparation techniques such as solid-phase extraction, liquid-liquid extraction, and rapid-fire techniques have also been discussed. This review will provide the detail information to the analytical manpower working in various quality control laboratories as well as in research organizations. HighlightsDetection of nitrosamine (NA) impurities in drug substances as well as finished products.HPLC, LC-MS/MS, and GC-MS/HS/AS discussed for the quantificationSolid-phase extraction, liquid-liquid extraction, and rapid-fire method for NA sample preparationMechanistic approach for nitrosamine formation and its removal strategiesRegulatory limits for NA impurities incorporated.

Simultaneous Method Development and Validation of Anastrozole Along with Piperine: Degradation Studies and Degradants Characterization Using LC-QTOF-ESI-MS Along with In-silico ADMET Predictions.

BACKGROUND: Anastrozole (ATZ) is a selective non-steroidal inhibitor widely used for the treatment of breast cancer in post-menopausal women. ATZ exerts its biological activity by inhibiting the enzyme aromatase, which is responsible for converting androgens to estrogens. Piperine (PIP), a natural alkaloid and the main component of black pepper, is used as a bioenhancer and for combating a variety of health issues ranging from upset stomach to dental problems. INTRODUCTION: ATZ has been reported to have poor water solubility and less bioavailability. The novel combination of ATZ and PIP was proposed to enhance the bioavailability of both the compounds. However, there are no reported studies on the simultaneous estimation of ATZ and PIP as well as stability studies to explore their potential interactions and degradation profiling. METHOD: A simple, accurate, precise, robust, sensitive, reliable, and economic analytical method for the simultaneous estimation of ATZ and PIP was developed using acetonitrile and water (60:40) as the mobile phase. Forced degradation studies and characterization of degradants were performed, and degradants were identified for molecular weight using LC-QTOF-ESI-MS; the structures of degradants were confirmed with mass accuracy measurements. The mechanism of each degradant has also been described in more detail in the manuscript. RESULTS AND CONCLUSION: A total of fourteen degradants were characterized and reported for their good human oral absorption. A precise, robust, accurate, cheap, and sensitive RP-HPLC-DAD simultaneous method for the estimation of ATZ and PIP has been developed. From the future point of view, there is huge scope to conduct pharmacological, pharmacodynamic, and drug-herb interaction studies based on this fruitful outcome. All the degradants may be screened against MDR-resistant breast cancer in the future to check their potential as a drug target.

UHPLC-DAD Method Development and Validation: Degradation Kinetic, Stress Studies of Farnesol and Characterization of Degradation Products Using LC-QTOF-ESI-MS with in silico Pharmacokinetics and Toxicity Predictions.

Farnesol (FAR) is a sesquiterpene molecule with high lipophilicity that has antibacterial and other pharmacological properties along with broad nutritional values with high commercial values. Although having potential, FAR stability behavior and degradation kinetics are not available in the literature. Hence, it is very essential to develop a simple, rapid, accurate, precise, robust, cheap UHPLC-DAD method for FAR. It was also proposed to study mechanistic insights into FAR under different degradation conditions. Therefore, we hypothesized to do systematic stability studies along with degradation kinetic and accelerated stability studies. The developed method was validated. FAR was studied for stress studies, degradation kinetics and ADMET prediction of degradants. Degradation products were characterized using LC-QTOF-ESI-MS. Developed method consists of an isocratic mobile phase with a wavelength of 215 nm. The percent recoveries for FAR were observed within the acceptance limit of 98-102%. The eight major degradation products were formed during stress studies. FAR follows first-order degradation kinetics. FAR and all degradants were found to have more than 75% good human oral absorption, and are non-toxic. FAR UHPLC-DAD method was developed, validated and performed stability studies to know the possible degradation pattern along with degradation kinetic studies.

Synthesis, characterisation and thermal studies of ruthenium(II) carbonyl complexes of functionalised tripodal phosphine chalcogen donor ligands, [CH(3)C(CH(2)P(X)Ph(2))(3)], where X=Se, S, O.

The polymeric ruthenium(II) carbonyl complex, [Ru(CO)(2)Cl(2)](n) reacts with 1,1,1-tris-(diphenylphosphinomethyl)ethane trichalcogenide ligands, [CH(3)C(CH(2)P(X)Ph(2))(3)], where X=Se(a), S(b) and O(c) in 1:1 (metal:ligand) molar ratio to afford hexa-coordinated complexes of the type eta(2)-(X,X)-[Ru(CO)(2)Cl(2)P(3)X(3)] (1a-c). The complexes 1a-c exhibit two equally intense nu(CO) bands in the range 1979-2060cm(-1) indicating cis-disposition of the two terminal carbonyl groups. The values of nu(CO) frequencies containing different ligands, in general, follow the order: P(3)O(3)>P(3)S(3)>P(3)Se(3) which may be explained in terms of 'Soft-Hard' (Ru(II)-O) and 'Soft-Soft' (Ru(II)-S/Se) interactions. The complexes have been characterized by elemental analyses, mass, (1)H, (31)P, (77)Se and (13)C NMR spectroscopy. The thermal stability of the complexes has also been studied.

Disseminated Histoplasmosis presenting as oropharyngeal mass lesion.

A 62 year old man from Silchar in North East India presented with complaints of painful swallowing, hoarseness, fever, anorexia and weight loss. Oropharyngeal examination revealed reddish ulcero-nodular lesion involving left tonsillar area and base of tongue which was clinically suspicious of malignancy. Radiological examination revealed involvement of bilateral adrenals by a mass. The biopsy of the oropharyngeal lesion showed many fungal spores morphologically favoring Histoplasmosis. Treatment with Amphotericin B followed by Itraconazole resulted recovery of lesions.

Selective Oxidation of Biomass-Derived Alcohols and Aromatic and Aliphatic Alcohols to Aldehydes with O2/Air Using a RuO2-Supported Mn3O4 Catalyst.

Selective catalytic oxidation of carbohydrate-derived 5-hydroxymethylfurfural, furfuryl alcohol, and various aromatic and aliphatic compounds to the corresponding aldehyde is a challenging task. The development of a sustainable heterogeneous catalyst is crucial in achieving high selectivity for the desired aldehyde, especially using O2 or air. In this study, a RuO2-supported Mn3O4 catalyst is reported for the selective oxidation reaction. Treatment of MnO2 molecular sieves with RuCl3 in aqueous formaldehyde solution gives a new type of RuO2-supported Mn3O4 catalyst. Detailed catalyst characterization using powder X-ray diffraction, N2 adsorption, scanning and transmission electron microscopes, diffuse reflectance UV-visible spectrometer, and X-ray photoelectron spectroscopy proves that the RuO2 species are dispersed on the highly crystalline Mn3O4 surface. This catalytic conversion process involves molecular oxygen or air (flow, 10 mL/min) as an oxidant. No external oxidizing reagent, additive, or cocatalyst is required to carry out this transformation. This oxidation protocol affords 2,5-diformylfuran, 2-formylfuran, and other aromatic and aliphatic aldehydes in good to excellent yield (70-99%). Moreover, the catalyst is easily recycled and reused without any loss in the catalytic activity.

Highly efficient and recyclable basic mesoporous zeolite catalyzed condensation, hydroxylation, and cycloaddition reactions.

Crystalline mesoporous ZSM-5 zeolite was prepared in the presence of 1,4-diazabicyclo[2.2.2]octane derived multi-cationic structure directing agent. The calcined form of the mesoprous zeolite was treated with NH4OH to obtain basic mesoporous ZSM-5. Catalyst was characterized by the complementary combination of X-ray diffraction, N2-adsorption, electron microscopes, and temperature programme desorption techniques. Catalytic activity of the basic mesoporous ZSM-5 was systematically assessed using Knoevenagel condensation reaction for the synthesis a wide range of substituted styrene. Applications of the catalyst were investigated in the benzamide hydroxylation for the synthesis of carbinolamides and one-pot, multi-component condensation reaction for the synthesis of naphthopyrans. Finally, the catalyst was evaluated in the cycloaddition of CO2 to epoxide for the synthesis of cyclic carbonates. Recycling study shows that no significant decrease in the catalytic activity was observed after five recycles.