Forced Degradation Study to Develop and Validate Stability-Indicating RP-LC for Quantification of Ropinirole Hydrochloride in Its Modified Release Tablets

A forced degradation study on ropinirole hydrochloride in bulk and in its modified release tablets was conducted under the conditions of hydrolysis, oxidation and photolysis in order to develop an isocratic stability-indicating LC-UV method for quantification of the drug in tablets. An impurity peak in standard solution was found to increase under acidic and neutral hydrolytic conditions while another degradation product was formed under alkaline condition. The drug and its degradation products were optimally resolved on a Hypersil C₁₈ column with mobile phase composed of diammonium hydrogen orthophosphate (0.05 M; pH 7.2), tetrahydrofuran and methanol (80:15:5% v/v) at a flow rate of 1.0 mL min^?1 at 30 °C using 250 nm as detection wavelength. The method was linear in the range of 0.05–50 μg mL^?1 drug concentrations. The %RSD of inter- and intra-day precision studies was <1. The system suitability parameters remained unaffected during quantification of the drug on three different LC systems. Excellent recoveries (101.59–102.28%) proved that the method was sufficiently accurate. The LOD and LOQ were found to be 0.012 and 0.040 μg mL^?1, respectively. Degradation behaviour of the drug in both bulk and tablets was similar. The drug was very unstable to hydrolytic conditions but stable to oxidative and photolytic conditions. The method can be used for rapid and accurate quantification of ropinirole hydrochloride in tablets during stability testing. Based on chemical reactivity of ropinirole in different media, the degradation products were suspected to be different from the known impurities of the drug.     

Determination of boron concentration in borosilicate glass,boron carbide and graphite samples by conventional wet-chemical and nuclear analytical methods

Boron is an important element in nuclear technology. A comparative study was carried out for the determination of boron in borosilicate glass, boron carbide and graphite samples by wet-chemical and nuclear analytical methods. Wet chemical methods namely titrimetry, Inductively Coupled Plasma Mass Spectrometry and ICP Optical Emission Spectrometry and nuclear analytical methods namely Particle Induced Gamma-Ray Emission and Nuclear Reaction Analysis were used. Boron concentrations were in trace (mg kg^?1) level in graphite and percentage level in borosilicate glass and boron carbide.     

Simultaneous determination of 14N and 15N isotopes in opium by proton induced γ-ray emission technique

The paper describes the simultaneous determination of ¹⁴N and ¹⁵N isotopes in opium by proton induced γ-ray emission (PIGE) technique. The isotopic ratio of ¹⁴N and ¹⁵N is a useful parameter for assigning provenance of (seized) illicit drugs. The measurement, non-destructive in nature, is performed on pellets made up of opium powders and is based on the prompt detection of 2.313 and 4.4 MeV γ-rays emanating from ¹⁴N(p,p′γ)¹⁴N and ¹⁵N(p,αγ)¹²C nuclear reactions respectively, induced simultaneously by 3.6–3.8 MeV proton beam. Positive as well as negative deviations from the natural isotopic abundance (99.63:0.37) were observed in the samples. The precision of the measurements is about 4%. The methodology provides an easy and rapid approach to determine the isotopic ratio of ¹⁴N and ¹⁵N and has been used for the first time in the analysis of opium.     

Design,synthesis and biological evaluation of 3-(2-aminooxazol-5-yl)-2<Emphasis Type="Italic">H</Emphasis>-chromen-2-one derivatives

Background

In view of wide range of biological activities of oxazole, a new series of oxazole analogues was synthesized and its chemical structures were confirmed by spectral data (Proton/Carbon-NMR, IR, MS etc.). The synthesized oxazole derivatives were screened for their antimicrobial and antiproliferative activities.

Results and discussion

The antimicrobial activity was performed against selected fungal and bacterial strains using tube dilution method. The antiproliferative potential was evaluated against human colorectal carcinoma (HCT116) and oestrogen- positive human breast carcinoma (MCF7) cancer cell lines using Sulforhodamine B assay and, results were compared to standard drugs, 5-fluorouracil and tamoxifen, respectively.

Conclusion

The performed antimicrobial activity indicated that compounds 3, 5, 6, 8 and 14 showed promising activity against selected microbial species. Antiproliferative screening found compound 14 to be the most potent compound against HCT116 (IC₅₀?=?71.8 µM), whereas Compound 6 was the most potent against MCF7 (IC₅₀?=?74.1 µM). Further, the molecular docking study has been carried to find out the interaction between active oxazole compounds with CDK8 (HCT116) and ER-α (MCF7) proteins indicated that compound 14 and 6 showed good dock score with better potency within the ATP binding pocket and may be used as a lead for rational drug designing of the anticancer molecule.

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Isocyanide insertion reactivity of dinuclear niobium and tantalum imido complexes: X-ray crystal structure of [{Nb(η-C5H4SiMe3)(CH2Ph)2}2(μ-1,4-NC6H4N)]

The reactivity of dinuclear niobium and tantalum imido complexes with the isocyanide compound 2,6-Me₂C₆H₃NC has been studied. The trialkyl complexes [{NbR₃(CH₃CN)}₂(μ-1,3-NC₆H₄N)], [{NbR₃(CH₃CN)}₂(μ-1,4-NC₆H₄N)] and [{TaR₃(CH₃CN)}₂(μ-1,4-NC₆H₄N)] (R=CH₂SiMe₃) gave [{Nb(η²-RCNAr)₂R}₂(μ-1,3-NC₆H₄N)] (1), [{Nb(η²-RCNAr)₂R}₂(μ-1,4-NC₆H₄N)] (2) and [{Ta(η²-RCNAr)₂R}₂(μ-1,4-NC₆H₄N)] (3) (R=CH₂SiMe₃; Ar=2,6-Me₂C₆H₃), from the isocyanide insertion in two of the metal alkyl carbon bonds. The reaction of the isocyanide reagent with the di-alkyl mono-cyclopentadienyl derivatives [{Nb(η⁵-C₅H₄SiMe₃)R₂}₂(μ-1,3-NC₆H₄N)] (R=Me, CH₂Ph, CH₂SiMe₃), [{Nb(η⁵-C₅H₄SiMe₃)R₂}₂(μ-1,4-NC₆H₄N)] (R=Me, CH₂Ph (4), CH₂SiMe₃) and [{Ta(η⁵-C₅Me₅)(CH₂SiMe₃)₂}₂(μ-1,4-NC₆H₄N)] yielded [{Nb(η⁵-C₅H₄SiMe₃)(η²-RCNAr)R}₂(μ-1,3-NC₆H₄N)] (R=Me (5), CH₂Ph (6), CH₂SiMe₃ (7)), [{Nb(η⁵-C₅H₄SiMe₃)(η²-RCNAr)R}₂(μ-1,4-NC₆H₄N)] (R=Me (8), CH₂Ph (9), CH₂SiMe₃ (10)) and [{Ta(η⁵-C₅Me₅)(η²-Me₃SiCH₂CNAr)CH₂SiMe₃}₂(μ-1,4-NC₆H₄N)] (11) (Ar=2,6-Me₂C₆H₃), respectively, from a single insertion process. The reaction with the mono-alkyl complex [{Nb(η⁵-C₅H₄SiMe₃)(Me)Cl}₂(μ-1,4-NC₆H₄N)] gave [{Nb(η⁵-C₅H₄SiMe₃)(η²-MeCNAr)Cl}₂(μ-1,4-NC₆H₄N)] (12), produced from the isocyanide insertion in the metal-alkyl carbon bond. The alkyl-amido complex [{Nb(η⁵-C₅H₄SiMe₃)(Me)NMe₂}₂(μ-1,4-NC₆H₄N)] gave, from the preferential isocyanide insertion in the metal-amide nitrogen bond, [{Nb(η⁵-C₅H₄SiMe₃)(η²-Me₂NCNAr)Me}₂(μ-1,4-NC₆H₄N)] (13). The molecular structure of one of the alkyl precursors, [{Nb(η⁵-C₅H₄SiMe₃)(CH₂Ph)₂}₂(μ-1,4-NC₆H₄N)] (4), has been determined.     

Transformation of 5‐Hydroxy‐ to (5‐Chloropentanoyl)amino Derivatives under ‘Direct Amide Cyclization’ Conditions

The application of the ‘direct amide cyclization’ conditions to the linear δ‐hydroxy diamide 11 is described (Scheme 3). Instead of the cyclization to the expected nine‐membered cyclodepsipeptide, only the chloro acid 12 was obtained. Its formation could be explained by consecutive formation of the 1,3‐oxazol‐5(4H)‐one 16 and the six‐membered imino lactone 17 as intermediates (Scheme 4). The spontaneous isomerization of the latter gave 12 in a good yield.     

Synthesis and reactivity of alkynyl niobocene complexes

The synthesis of alkynyl containing niobocene complexes with differing auxiliary ligands is described. The niobium(III) derivatives of the general formula [Nb(η⁵-C₅H₄SiMe₃)₂(CCR)(L)] where L is either carbonyl, phosphine, phosphite, or isocyanide, were prepared by the reaction of the bis(alkynyl)magnesium reagent with the corresponding cloro-niobocene precursor. In a similar manner the niobium(V) imido compounds, of the general formula, [Nb(=NR′)(η⁵-C₅H₄R″)₂(CCR)], were prepared. The characterization of these complexes is discussed. The reactivity of the alkynyl compounds towards oxidation and protonation has been studied.     

Synchrotron radiation induced X‐ray production cross sections of 66Dy at energies across its Li (i = 1–3) subshell absorption edges

The X‐ray production (XRP) cross sections for the ₆₆Dy L_k (k = l, α, η, β_2,6,7,15, β_1,6, β_1,3,4,6, β_2,7,15, γ_1,5, γ₂,₃) emission lines have been measured by tuning the incident synchrotron radiation at energies over the range 7.8–9.2 keV and ~10–370 eV above the respective L_i (i = 1–3) absorption edges. These measurements aim to check the reliability of the independent particle approximation models used to generate the theoretical data sets of different physical parameters required to calculate the XRP cross sections and also investigate the influence of many body effects on the photoionization process. The measured values have been compared with 4 sets of XRP cross sections calculated using the Dirac–Fock model‐based X‐ray emission rates, 2 sets of the L_i (i = 1–3) subshell photoionization cross sections deduced from the self‐consistent Dirac–Hartree–Fock model‐based values and the nonrelativistic Hartree–Fock–Slater model‐based values, and 2 sets of the fluorescence (ω_i) and Coster–Kronig (f_ij) yields. The present measured Lγ_2,3 (originating from decay of the L₁ subshell vacancies) XRP cross sections are found to be significantly higher than different sets of theoretical values, whereas a good agreement is generally observed for the various other XRP cross sections and relative intensities.