A novel UPLC-PDA isocratic method for the quantification fulvestrant in oil-based pre-filled syringe injection matrix formulations

Abstract Background Fulvestrant is a new estrogen receptor antagonist available in the market globally for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women. Methods The chromatographic separation of fulvestrant was carried out by using ACQUITY UPLC and a BEH Shield RP18, 50 mm × 2.1 mm, i.d 1.7-μm column with a prepared mobile phase consisting of water, acetonitrile, and methanol in the ratio of 300:400:300 (v/v/v), respectively. 1.0 mL orthophosphoric acid was added to the prepared mobile phase. The wavelength for detection was made at 220.0 nm using a PDA-UV detector with a flow rate of 0.3 mL min− 1. Results The system suitability parameters were found within the limits. The coefficient of correlation was found not less than 0.999. The percent recoveries of fulvestrant from 80, 100, to 120% levels are 100.1, 100.4, and 99.7 respectively. The LOD (0.51 μg mL− 1) and LOQ (1.54 μg mL− 1) values from the study demonstrate that the method is sensitive. The samples were subjected to forced degradation conditions of acidic and alkaline hydrolysis, oxidation, photolysis, metallic and thermal degradation in all conditions; peak was found pure (purity angle less than that of threshold). Conclusion A rapid, simple, stability-indicating, and validated RP-UPLC method was developed with 6 min of run time for the quantification of fulvestrant in oil-based injection formulations. This is the first stability-indicating method with the capability of resolving all the fulvestrant degradation impurities in the drug products. The method was validated for system suitability, linearity, precision, accuracy, specificity, intermediate precision, ruggedness, robustness, and solution stability

Simple one-pot green method for large-scale production of mesalamine, an anti-inflammatory agent

We report a rapid and efficient synthesis protocol for mesalamine via a green approach with 2-chloro-5-nitrobenzoic acid as the starting material, for its large-scale production. This one-pot method involves the conversion of a chloro group into a hydroxyl group using aqueous KOH solution, followed by the reduction of a nitro group to amine using Pd/C. The product was characterised and confirmed by 1H-nuclear magnetic resonance (NMR), 13C NMR, IR and mass spectrometry techniques. The salient features of the method include excellent conversion (99.3%), high yield (93%), cost effectiveness and validated results for benign, large-scale production

Electrochemical performance of SnO–V2O5–SiO2 glass anode for Na-ion batteries

Abstract SnO–V2O5–SiO2 glass anode sample prepared by simple a mechanical milling technique. The amorphous nature of sample identified using with XRD technique. This glass anode has an initial charge capacity of 560 mAhg−1 and discharge capacity of 483 mAhg−1. After 20 charge–discharge cycles, charge and discharge capacities achieved to be 389 and 379 mAhg−1 at 0.1C, respectively. The loss in discharge capacity is up to ~ 45.22% even at high rate 5C

Simultaneous estimation of silodosin and silodosin β-D-glucuronide in human plasma using LC-MS/MS for a pharmacokinetic study

A rapid, simple, sensitive and selective LC-MS/MS method has been developed and validated for simultaneous quantification of silodosin and silodosin β-D-glucuronide human plasma using stable labelled isotopes as internal standards. Solid phase extraction technique (SPE) was used for the extraction and the method validated over a range of 0.20 ng/mL to 100.56 ng/mL for silidisin and 0.20 ng/mL to 101.63 ng/mL for silodosin β-D-glucuronide. The chromatographic separation was achieved on Cosmicsil Adze C18 (4.6 × 100 mm, 3 µm) column using a mobile phase consisting of acetonitrile, methanol and 10 mM ammonium acetate buffer 50:20:30 (v/v/v) at a flow rate of 1.000 mL/min with run time of 4 min. The API-4500 LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. The developed assay method was successfully applied to a pharmacokinetic study in humans

Isolation, identification, structural elucidation, and toxicity prediction using (Q)-SAR models of two degradants: AQbD-driven LC method to determine the Roxadustat impurities

ABSTRACT: Roxadustat (RDT) is the first orally administrated HIF-prolyl hydroxylase inhibitor drug used to treat anemia caused by chronic kidney disease. Two unknown degradants were detected in photolytic and oxidative stress conditions during the forced degradation study of RDT and isolated them using the preparative HPLC. The structural characterization of these impurities was confirmed using ESI-LC-MS, NMR, and FT-IR spectroscopic analysis. To evaluate the toxicity of degradants, (Q)-SAR models such as Derek and Sarah model were utilized. The current study aims to develop a stability-indicating related substances quantification method in RDT along with degradant impurities by implementing AQbD principles. The Box-Behnken Design (BBD) was utilized to optimize the final analytical method conditions. p-values for the model and lack of fit were 0.05, respectively. The optimized CMPs are 30:70 (v/v) ACN: Methanol in mobile phase-B, 50:50 mobile phase-A & B in the initial gradient program, 0.95 mL/min of flow rate, and 40 °C as column oven temperature. Agilent Zorbax XDB-C8, (250 × 4.6) mm, 5 μm analytical column was used to separate the desired components from the sample matrix peaks and themselves. The optimized method was validated in compliance with regulatory requirements. The recoveries for all the impurities ranged from 96.8% to 99.7%, with an%RSD 0.998. The current method can be used in quality-control laboratories to quantify RDT impurities without any developmental trials

Design, synthesis and in silico docking techniques of new 1,2,3-triazolylpyrrolidines bearing chalcone derivatives: Discovery of potent antitubercular agents

Compounds with a pyrrolidine scaffold play an important role in organic synthesis and especially in the synthesis of bioactive organic compounds, therefore, the development of new methods for modifying this scaffold is a very interesting framework of this study. We developed a rational approach for the synthesis of 1,2,3-trazolylchalcone substituted pyrrolidines derivatives, which were then examined using a variety of spectroscopic techniques such as 1H NMR, 13C NMR, FT-IR, mass spectroscopy and elemental analysis. Biological profiles showed that compounds 5e, 5h had better antibacterial inhibitory potency against S. aureus, E. coli with zone of inhibition 34 ± 0.1, 33 ± 0.3 mm, whereas 5a, 5e showed potent antifungal activity against C. parapsilosis, A. flavus with dimeter zone of inhibition 26 ± 0.2, and 30 ± 0.2 mm respectively. Among the tested compounds 5b, and 5h were the most potent antitubercular activity against Mycobacterium tuberculosis H37Rv and showing MIC values 5.23 µg/mL, 6.85 µg/mL respectively, which are similar activity that of the standard Streptomycin (MIC = 5.02 µg/mL). The binding mode for compound 5 inside the catalytic pocket of M. tuberculosis cytochrome P450 CYP121A1 and produced a network of hydrophobic and hydrophilic interactions (6GEO). From docking results, 5b demonstrated highly stable binding amino acids SerA:237, ArgA:386, ArgA:286, CysA:345, MetA:62, GlnA:385, AspA:282, PheA:280, LeuA:284, ValA:83, ProA:285, AlaA:337, HisA:343, AsnA:74, and ThrA:65, which are plays a crucial role in ensuring efficient binding of the ligand in a crystal structure of tubercular receptor. Furthermore, the physicochemical and ADME (absorption, distribution, metabolism, and excretion) filtration molecular properties, estimation of toxicity, and bioactivity scores of these scaffolds were evaluated

Design, synthesis, anticancer evaluation and molecular docking studies of 1,2,3-triazole incorporated 1,3,4-oxadiazole-Triazine derivatives

A new library of 1,2,3-triazole-incorporated 1,3,4-oxadiazole-triazine derivatives (9a-j) was designed, synthesized, and tested in vitro for anticancer activity against PC3 and DU-145 (prostate cancer), A549 (lung cancer), and MCF-7 (breast cancer) cancer cell lines using the MTT assay with etoposide as the control drug. The compounds exhibited remarkable anticancer activity, with IC50 values ranging from 0.16 ± 0.083 μM to 11.8 ± 7.46 μM, whereas the positive control ranged from 1.97 0.45 μM to 3.08 0.135 μM. Compound 9 d with a 4-pyridyl moiety shown exceptional anticancer activity against PC3, A549, MCF-7, and DU-145 cell lines, with IC50 values of 0.17 ± 0.063 μM, 0.19 ± 0.075 μM, 0.51 ± 0.083 μM, and 0.16 ± 0.083 μM, respectively