ABSTRACT
Vapor-induced transformations of docetaxel anhydrous (form D(A)) under ambient conditions have been studied using methanol, ethanol, and water as the solvent media. The online vapor-induced transformations were monitored by powder X-ray diffractometry. New solid forms (solvates/hydrates/anhydrous) of docetaxel anhydrous were obtained in stoichiometric ratios which were characterized completely using powder X-ray diffraction, differential scanning calorimeter, thermogravimetric analysis, and spectroscopic ((13)C solid-state nuclear magnetic spectroscopy, solution (1)H NMR, and Fourier transform infrared) techniques. The new forms namely methanol solvate (D(M)), ethanol solvate (D(E)), monohydrate (D(MH)), trihydrate (D(TH)), and anhydrous (D(AN-I) and D(AN-II)) were identified through structural analysis.
Subject(s)
Antineoplastic Agents/chemistry , Phase Transition , Taxoids/chemistry , Calorimetry, Differential Scanning , Chemistry, Pharmaceutical , Crystallography, X-Ray , Docetaxel , Ethanol/chemistry , Magnetic Resonance Spectroscopy , Methanol/chemistry , Molecular Structure , Powder Diffraction , Solvents/chemistry , Spectroscopy, Fourier Transform Infrared , Technology, Pharmaceutical/methods , Thermogravimetry , Volatilization , Water/chemistryABSTRACT
Five unknown impurities ranging from 0.05 to 0.2% in donepezil were detected by a simple isocratic reversed-phase high performance liquid chromatography (HPLC). These impurities were isolated from crude sample of donepezil using isocratic reversed-phase preparative high performance liquid chromatography. Based on the spectral data (IR, NMR and MS), the structures of these impurities were characterised as 5,6-dimethoxy-2-(4-pyridylmethyl)-1-indanone (impurity I), 4-(5,6-dimethoxy-2,3-dihydro-1H-2-indenylmethyl) piperidine (impurity II), 2-(1-benzyl-4-piperdylmethyl)-5,6-dimethoxy-1-indanol (impurity III) 1-benzyl-4(5,6-dimethoxy-2,3-dihydro-1H-2-indenylmethyl) piperidine (impurity IV) and 1,1-dibenzyl-4(5,6-dimethoxy-1-oxo-2,3-dihydro-2H-2-indenylmethyl)hexahydropyridinium bromide (impurity V). The synthesis of these impurities and their formation was discussed.
Subject(s)
Indans/chemistry , Piperidines/chemistry , Cholinesterase Inhibitors/chemistry , Chromatography, High Pressure Liquid/methods , Donepezil , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Structure , Spectroscopy, Fourier Transform InfraredABSTRACT
Acid, base and oxygen stability of risperidone, a novel anti-psychotic drug, has been evaluated storing the sample in solution phase. One of the major degradation products has been identified and characterized by using techniques namely IR, MS and NMR after isolation by preparative LC. The other major degradation product has been identified with help of MS/MS data and by co-eluting in analytical LC with the available standard. The effect of acid and base resulted in the formation of hydroxy risperidone and the effect of oxygen lead to the formation of N-oxide of risperidone. The two major degradation products in the dosage forms were also characterized as 9-hydroxy risperidone and N-oxide of risperidone, after enrichment through preparative LC, by LC-MS/MS and HPLC. Structural elucidation of degradation product leading to the formation of N-oxide of risperidone is discussed in detail.
Subject(s)
Pharmaceutical Preparations/analysis , Risperidone/analysis , Chromatography, Liquid , Drug Stability , Hydrochloric Acid/chemistry , Mass Spectrometry , Molecular Structure , Oxidation-Reduction , Peroxides/chemistry , Pharmaceutical Preparations/chemistry , Pharmaceutical Preparations/standards , Risperidone/chemistry , Risperidone/standards , Sodium Hydroxide/chemistryABSTRACT
Two unknown impurities in linezolid bulk drug at levels below 0.1% (ranging from 0.05 to 0.1%) were detected by a simple isocratic reverse phase high performance liquid chromatography (HPLC). These impurities were isolated from crude sample of linezolid using reverse phase preparative HPLC. Based on the spectroscopic data (IR, NMR and MS) the structures of the impurities were characterized as (S)-N-[[-(3-(3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl] acetate(I) and (S)-N-[[-(3-(3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl] chloride(II). The synthesis from an unambiguous route and the formation of impurities was discussed.
Subject(s)
Acetamides/isolation & purification , Drug Contamination , Oxazolidinones/isolation & purification , Acetamides/chemistry , Chromatography, High Pressure Liquid/methods , Linezolid , Oxazolidinones/chemistry , Technology, Pharmaceutical/methodsABSTRACT
Two unknown impurities in rofecoxib bulk drug at levels below 0.1% were detected by a simple isocratic reverse phase high performance liquid chromatography (HPLC). These impurities were isolated from crude sample of rofecoxib using reverse phase preparative HPLC. (1)H, (13)C and Mass spectroscopic investigations revealed the structures of the impurities as 4-[4-(methylsulphonyl)phenyl]-3-phenyl-5-hydroxyfuran-2-one (I) and 4-[4-(methylsulphonyl)phenyl]-3-phenyl-2,5-furandione (II), respectively. These structures were further confirmed by prepared synthetic standards of the impurities. The tentative mechanism for the formation of these impurities was discussed.
