Identification and structural elucidation of two process impurities and stress degradants in darifenacin hydrobromide active pharmaceutical ingredient by LC-ESI/MS(n).

The present study describes the identification and characterization of two process impurities and major stress degradants in darifenacin hydrobromide using high performance liquid chromatography (HPLC) analysis. Forced degradation studies confirmed that the drug substance was stable under acidic, alkaline, aqueous hydrolysis, thermal and photolytic conditions and susceptible only to oxidative degradation. Impurities were identified using liquid chromatography coupled with ion trap mass spectrometry (LC-MS/MS(n)). Proposed structures were unambiguously confirmed by synthesis followed by characterization using nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR) and elemental analysis (EA). Based on the spectroscopic, spectrometric and elemental analysis data, the unknown impurities were characterized as 2-{1-[2-(2,3-dihydrobenzofuran-5-yl)-2-oxo-ethyl]-pyrrolidin-3-yl}-2,2-diphenylacetamide (Imp-A), 2-[1-(2-benzofuran-5-yl-ethyl)-pyrrolidin-3-yl]-2,2-diphenylacetamide (Imp-B), 2-{1-[2-(2,3-dihydrobenzofuran-5-yl)-ethyl]-1-oxy-pyrrolidin-3-yl}-2,2-diphenylacetamide (Imp-C) and 2-{1-[2-(7-bromo-2,3-dihydrobenzofuran-5-yl)-ethyl]-pyrrolidin-3-yl}-2,2-diphenylacetamide (Imp-D). Plausible mechanisms for the formation and control of these impurities have also been proposed. The method was validated as per regulatory guidelines to demonstrate specificity, sensitivity, linearity, precision, accuracy and the stability-indicating nature. Regression analysis showed a correlation coefficient value greater than 0.99 for darifenacin hydrobromide and its impurities. The accuracy of the method was established based on the recovery obtained between 86.6 and 106.7% for all impurities.

A novel online approach to the determination of isotopic ratios for organically bound chlorine, bromine and sulphur.

A novel approach for the measurement of (37)Cl, (81)Br and (34)S in organic compounds containing chlorine, bromine, and sulphur is presented to overcome some of the major drawbacks of existing methods. Contemporary methods either require reference materials with the exact molecular compositions of the substances to be tested, or necessitate several laborious offline procedures prior to isotope analysis. In our online setup, organic compounds are separated by gas chromatography (GC) coupled to a high-temperature reactor. Using hydrogen as a makeup gas, the reactor achieves quantitative conversion of chlorinated, brominated and sulphurated organic compounds into gaseous hydrogen chloride (HCl), hydrogen bromide (HBr), and hydrogen sulphide (H(2)S), respectively. In this study, the GC interface was coupled to a quadrupole mass spectrometer operated in single-ion mode. The ion traces of either H(35)Cl (m/z 36) and H(37)Cl (m/z 38), H(79)Br (m/z 80) and H(81)Br (m/z 82), or H(2)(32)S (m/z 34) and H(2)(34)S (m/z 36), were recorded to determine the isotopic ratios of chlorine, bromine, and sulphur isotopes. The conversion interface presented here provides a basis for a novel method for compound-specific isotope analysis of halogenated and sulphur-containing compounds. Rapid online measurements of organic chlorine-, bromine- and sulphur-containing mixtures will facilitate the isotopic analysis of compounds containing these elements, and broaden their usage in fields of environmental forensics employing isotopic concepts.

Pyrolysis of waste electrical and electronic equipment: effect of antinomy trioxide on the pyrolysis of styrenic polymers.

This work has investigated the effect that antimony trioxide has on the pyrolysis of styrenic polymers and the effect that different types of brominated flame retardants used in plastics have on the composition of the pyrolysis products. Brominated high impact polystyrene (Br-HIPS) which contained either 5% or 0% antimony trioxide and either decabromodiphenyl oxide (DDO) or decabromodiphenyl ethane (DDE) was pyrolysed in a fixed bed reactor at 430 degrees C. Some experiments on the fixed bed reactor involved mixing the Br-HIPS with polystyrene. The gaseous products were analysed by GC-FID and GC-TCD and it was found that antimony trioxide caused an increase in the proportion of ethane and ethene and suppressed the proportion of butane and butene. When DDE was the flame retardant increased proportions of ethane and ethene were found in the pyrolysis gas compared to when DDO used. When polystyrene was mixed with the Br-HIPS it suppressed the trends observed in the gas composition during the pyrolysis of Br-HIPS. The pyrolysis oils were characterised using FT-IR, GC-MS, GC-FID, and GC-ECD. It was found that the plastic which did not contain antimony trioxide pyrolysed to form mainly toluene, ethylbenzene, styrene, cumene, and alpha-methylstyrene. The oils produced from the pyrolysis of the plastic that contained antimony trioxide did not contain any styrene or alpha-methylstyrene, but instead contained greater concentrations of ethylbenzene and cumene. The absence of styrene and alpha-methylstyrene from the pyrolysis oil occurred even when the Br-HIPS was mixed with polystyrene. GC-ECD analysis of the oils showed that the plastics which did not contain antimony trioxide pyrolysed to form (1-bromoethyl)benzene, which was totally absent from the pyrolysis oils when antimony trioxide was present in the plastic.