ABSTRACT
A new process impurity was detected during the HPLC analysis of Tizanidine hydrochloride (I) batches. The impurity (II) was isolated by preparative HPLC and characterized by NMR and Mass spectral analysis as 5-S-ethyl-N-(4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothiadiazol-4-amine hydrochloride.
ABSTRACT
A sensitive, precise, specific, linear and stability indicating isocratic HPLC method was developed for the analysis of related substances in zolmitriptan. The potential known related substances are (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (impurity I) and (S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one (impurity II). The method can be used for the detection and quantification of known and unknown impurities and degradants in the drug substance zolmitriptan during routine analysis and also for stability studies in view of its capability to separate degradation products.
ABSTRACT
A gradient reversed phase HPLC method was developed and validated for the analysis of related substances in zonisamide (1,2-benzisoxazole-3-methanesulfonamide), using a Waters Symmetry C8 (150*3.9 mm) column with a flow rate of 1.0 ml/min and detection at 280 nm. The mobile phase component A consisted of a mixture of 0.02 M aqueous potassium dihydrogen phosphate-acetonitrile-methanol (75:10:15 v/v/v), pH adjusted to 4.0 with orthophosphoric acid. The mobile phase component B consisted of a mixture of 0.02 M aqueous potassium dihydrogen phosphate-acetonitrile-methanol (15:40:45 v/v/v), pH 2.0 with orthophosphoric acid. The limit of detection and limit of quantitation were in the range of 0.001-0.007% and 0.0035-0.25% respectively with respect to sample concentration of 2 mg/ml. The method was linear in the range of LOQ level to 200% of specified limits for II-VIII (< 0.10%, r(2)= 0.9958-0.9999). The method is sensitive, specific, linear, accurate, precise and stability-indicating for the detection and quantitation of precursors (viz., 4-hydroxycoumarin, 1,2-benzisoxazole-3-acetic acid, 1,2-benzisoxazole-3-bromoacetic acid, 1,2-benzisoxazole-3-methylbromide, sodium 1,2-benzisoxazole-3-methanesulfonate), process impurities (viz., 2-hydroxyacetophenone oxime and 3,3,3-tribromomethyl-1,2-benzisoxazole) and drug degradation products formed under stress conditions.
Subject(s)
Alkenes/isolation & purification , Antifungal Agents/isolation & purification , Cyclohexanes/isolation & purification , Fungi/metabolism , Alkenes/chemistry , Alkenes/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Cyclohexanes/chemistry , Cyclohexanes/pharmacology , Fermentation , Fungi/chemistry , Gas Chromatography-Mass Spectrometry , Microbial Sensitivity Tests , Nuclear Magnetic Resonance, Biomolecular , Optical Rotation , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , StereoisomerismABSTRACT
Two novel compounds, kodaistatin A, C35H34O11, molecular weight 630, and kodaistatin C, C35H34O12, molecular weight 646, have been isolated from cultures of Aspergillus terreus Thom DSM 11247 by solid-phase extraction, size-exclusion chromatography, and various preparative HPLC steps. The use of a range of 2D NMR measurements, in particular 13C-13C correlation measurements, has led to the clarification of the structure of kodaistatin A. Kodaistatin C is a hydroxylated derivative of kodaistatin A. Both natural products contain hydroxylated aspulvinones and identical highly substituted polyketide units. An X-ray single crystal structure analysis of aspulvinon E demonstrated the z-configuration at the central double bond. The kodaistatins are effective inhibitors of the glucose-6-phosphate translocase component of the glucose-6-phosphatase system (EC 3.1.3.9), an enzyme system which is important for the control of blood glucose levels. The IC50 is 80 nM for kodaistatin A and 130 nM for kodaistatin C.
Subject(s)
Aspergillus/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Phosphotransferases/antagonists & inhibitors , Animals , Antiporters , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/enzymology , Enzyme Inhibitors/isolation & purification , Inhibitory Concentration 50 , Lactones/chemistry , Lactones/isolation & purification , Lactones/pharmacology , Liver/drug effects , Liver/enzymology , Magnetic Resonance Spectroscopy , Mass Spectrometry , Microsomes, Liver/drug effects , Microsomes, Liver/enzymology , Molecular Structure , Monosaccharide Transport Proteins , RatsSubject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/metabolism , Antifungal Agents/chemistry , Antifungal Agents/metabolism , Ascomycota/metabolism , Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Bacteria/drug effects , Fungi/drug effects , Magnetic Resonance Spectroscopy , Molecular Structure , Spiro Compounds/chemistry , Spiro Compounds/metabolism , Spiro Compounds/pharmacologyABSTRACT
Arthrichitin (1), C(33)H(46)N(4)O(9), is a new cell wall active depsipeptide isolated from the fermentation broth of Arthrinium phaeospermum (HIL Y-903022). Its structure was elucidated on the basis of spectroscopic and chemical degradation studies. Arthrichitin consists of serine, beta-keto tryptophan, glutamic acid, and 2,4-dimethyl-3-hydroxydodecanoic acid units.
Subject(s)
Actinomycetales/metabolism , Antifungal Agents/isolation & purification , Antifungal Agents/chemistry , Chemical Phenomena , Chemistry, Physical , Chromatography, High Pressure Liquid , Fermentation , Magnetic Resonance Spectroscopy , Molecular Structure , Pyrans/chemistry , Pyrans/isolation & purificationSubject(s)
Anti-Bacterial Agents/isolation & purification , Streptomyces/metabolism , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Chemical Phenomena , Chemistry, Physical , Gram-Positive Bacteria/drug effects , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Molecular Structure , Phenazines/chemistry , Phenazines/isolation & purification , Phenazines/pharmacology , Spectrophotometry, InfraredSubject(s)
Anti-Bacterial Agents/chemistry , Peptides , Pseudomonas/drug effects , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides , Chemical Phenomena , Chemistry, Physical , Molecular Structure , Nucleosides , Streptomyces/chemistryABSTRACT
A new glycopeptide antibiotic, balhimycin, has been isolated from the fermentation broth of a Amycolatopsis sp. Y-86,21022. Balhimycin belongs to the vancomycin class of glycopeptides and contains a dehydrovancosamine sugar. The biological activity of balhimycin has been compared extensively with that of vancomycin against methicillin resistant staphylococci and also against anaerobes. Balhimycin is marginally superior to vancomycin in its in vitro activity against anaerobes and in its bactericidal properties.
Subject(s)
Anti-Bacterial Agents , Vancomycin/analogs & derivatives , Actinobacteria/classification , Actinobacteria/metabolism , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Blood Proteins/metabolism , Drug Resistance, Microbial , Fermentation , Microbial Sensitivity Tests , Protein Binding , Staphylococcus/drug effects , Vancomycin/biosynthesis , Vancomycin/chemistry , Vancomycin/isolation & purification , Vancomycin/metabolism , Vancomycin/pharmacologyABSTRACT
Two new secondary metabolites, aranorosinol A (1) and aranorosinol B (2), were isolated from a strain of Pseudoarachniotus roseus. Their structures were elucidated on the basis of their spectral properties and chemical transformations and were found to be similar to aranorosin (3) isolated from the same strain.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Fatty Acids, Unsaturated/chemistry , Fatty Acids, Unsaturated/isolation & purification , Spiro Compounds/chemistry , Spiro Compounds/isolation & purification , Anti-Bacterial Agents/pharmacology , Ascomycota/chemistry , Bacteria/drug effects , Chromatography, Gel , Fatty Acids, Unsaturated/pharmacology , Fungi/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Microbiological Techniques , Spiro Compounds/pharmacology , Structure-Activity RelationshipABSTRACT
Alisamycin is a new member of the manumycin group of antibiotics produced by Streptomyces sp. HIL Y-88,31582, which taxonomically appears to be Streptomyces actuosus. Alisamycin is active against Gram-positive bacteria and fungi, and has a weak antitumour activity.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/pharmacology , Fermentation , Microbial Sensitivity Tests , Polyenes/isolation & purification , Polyenes/pharmacology , Streptomyces/classification , Streptomyces/metabolismABSTRACT
Butalactin, [2-(4',5'-epoxy-hex-2'(E)-en)oyl-2-hydroxy-3-hydroxymethyl-2, 3-(Z)-butanolide] is a new antibiotic produced by Streptomyces sp. HIL Y-86,36923. Taxonomically, the producing organism most closely resembles Streptomyces corchorusii. The strain also produces cineromycin B. Though butalactin is structurally related to 'signal molecules' such as A-factor, the anthracycline inducing factors and the virginiae butanolides, it does not show inducing activity for antibiotic production or aerial mycelium formation in the indicator strain. Butalactin possesses a weak antibiotic activity against Gram-positive and Gram-negative bacteria.
Subject(s)
Anti-Bacterial Agents/biosynthesis , Streptomyces/metabolism , 4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/isolation & purification , 4-Butyrolactone/metabolism , 4-Butyrolactone/pharmacology , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Chromatography, Thin Layer , Culture Media , Fermentation , Microscopy, Electron , Soil Microbiology , Spores, Bacterial/ultrastructure , Streptomyces/classification , Streptomyces/drug effects , Streptomyces/ultrastructure , Streptomycin/biosynthesisABSTRACT
Aranorosin, a new antifungal antibiotic, has been isolated from the culture filtrate and mycelium of a strain of Pseudoarachniotus roseus Kuehn. The antibiotic, C23H33NO6, contains a novel 1-oxaspiro[4,5]decane ring system. The structure (I) has been elucidated on the basis of spectroscopic and chemical analysis.
