ABSTRACT
A novel stability-indicating high-performance liquid chromatographic assay method was developed and validated for docetaxel in the presence of degradation products generated from forced decomposition studies. A gradient HPLC method was developed to separate the drug from the degradation products, using a Hichrom RPB HPLC column. Mixture of water and acetonitrile was used as mobile phase. The flow rate was 1.0 ml/min and the detection was done at 230 nm. Using the above method one can carry out the quantitative estimation of impurity namely DCT-1 and docetaxel. The developed gradient LC method was subsequently validated.
Subject(s)
Antineoplastic Agents, Phytogenic/analysis , Chromatography, High Pressure Liquid/methods , Taxoids/analysis , Antineoplastic Agents, Phytogenic/chemistry , Docetaxel , Drug Stability , Reproducibility of Results , Taxoids/chemistry , Technology, PharmaceuticalABSTRACT
The present paper describes the development of a stability indicating high performance liquid chromatographic (HPLC) assay method for zoledronic acid in the presence of its impurities and degradation products generated from forced decomposition studies. The drug substance was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. The degradation of zoledronic acid was observed under oxidative stress at higher temperature. The drug was found to be stable in other stress conditions attempted. Successful separation of the drug from the degradation products formed under stress conditions was achieved on a C18 column using a mixture of phosphate buffer that contains 7 mM tetra butyl ammonium hydrogen sulphate, an ion-pairing agent and methanol (95:5) as mobile phase. The developed HPLC method was validated with respect to response function, precision, accuracy, specificity and robustness. The developed HPLC method to determine the related substances and assay determination of zoledronic acid can be used to evaluate the quality of regular production samples. It can be also used to test the stability samples of zoledronic acid.
Subject(s)
Bone Density Conservation Agents/chemistry , Chemistry, Pharmaceutical/methods , Chromatography, High Pressure Liquid/methods , Diphosphonates/chemistry , Drug Stability , Imidazoles/chemistry , Bone Density Conservation Agents/analysis , Calibration , Chromatography , Diphosphonates/analysis , Drug Contamination , Drug Industry/methods , Hot Temperature , Hydrolysis , Imidazoles/analysis , Ions , Light , Models, Chemical , Oxygen/analysis , Pharmaceutical Solutions/chemistry , Phenylcarbamates/analysis , Reproducibility of Results , Sensitivity and Specificity , Temperature , Zoledronic AcidABSTRACT
A new and accurate chiral liquid chromatographic method was developed for the enantiomeric resolution of Rivastigmine hydrogen tartarate, (-)S-N-ethyl-3-[(1-dimethyl-amino)ethyl]-N-methylphenyl-carbamate hydrogen tartarate, a cholinesterase inhibitor in bulk drugs. The enantiomers of Rivastigmine hydrogen tartarate were baseline resolved on a Chiralcel OD-H (250 mm x 4.6 mm, 5 microm) column using a mobile phase system containing hexane: isopropanol: trifluoroacetic acid (80:20:0.2, v/v/v). The resolution between the enantiomers was not less than four and interestingly distomer was eluted prior to eutomer in the developed method. The presence of trifluoroacetic acid in the mobile phase has played an important role in enhancing chromatographic efficiency and resolution between the enantiomers. The developed method was extensively validated and proved to be robust. The limit of detection and limit of quantification of (R)-enantiomer were found to be 500 and 1500 ng/ml, respectively for 10 microl injection volume. The percentage recovery of (R)-enantiomer was ranged from 95.2 to 104.3 in bulk drug samples of Rivastigmine hydrogen tartarate. Rivastigmine hydrogen tartarate sample solution and mobile phase were found to be stable for at least 48 h. The proposed method was found to be suitable and accurate for the quantitative determination of (R)-enantiomer in bulk drugs. Chiralcel OJ-H column can also be used as an alternative for the above purpose.
Subject(s)
Cholinesterase Inhibitors/isolation & purification , Chromatography, High Pressure Liquid/methods , Phenylcarbamates/isolation & purification , Cholinesterase Inhibitors/analysis , Cholinesterase Inhibitors/chemistry , Chromatography, High Pressure Liquid/instrumentation , Phenylcarbamates/analysis , Phenylcarbamates/chemistry , Reproducibility of Results , Rivastigmine , StereoisomerismABSTRACT
A new and accurate chiral liquid chromatographic method was described for the enantiomeric separation of ZTR-5 [(4S)-4-(4-aminobenzyl)-2-oxazolidinone, (S)-isomer], a key intermediate of Zolmitriptan in bulk drugs. The enantiomers of ZTR-5 were baseline resolved on a Chiralpak AD-H (250 mm x 4.6 mm, 5 microm) column using a mobile phase system containing hexane:ethanol (70:30, v/v). The resolution between the enantiomers was not less than four and interestingly distomer was eluted prior to eutomer. The limit of detection and limit of quantification of (4R)-4-(4-aminobenzyl)-2-oxazolidinone [(R)-isomer] were found to be 250 and 750 ng/ml, respectively, for 10 microl injection volume. The percentage recovery of (R)-isomer ranged from 92.0 to 105.6 in the bulk drug samples of ZTR-5. The validated method yielded good results regarding precision, linearity, accuracy and ruggedness. The proposed method was found to be suitable and accurate for the quantitative determination of (R)-isomer in bulk drug samples of ZTR-5.
Subject(s)
Chemistry, Pharmaceutical/methods , Chromatography, Liquid/instrumentation , Chromatography, Liquid/methods , Oxazolidinones/analysis , Oxazolidinones/pharmacology , Tryptamines/analysis , Tryptamines/pharmacology , Amylose/analogs & derivatives , Amylose/chemistry , Chromatography , Chromatography, High Pressure Liquid , Drug Industry/methods , Isomerism , Models, Chemical , Molecular Structure , Oxazolidinones/chemistry , Phenylcarbamates/chemistry , Reproducibility of Results , Sensitivity and Specificity , Spectrophotometry, Ultraviolet/methods , Stereoisomerism , Time Factors , Tryptamines/chemistryABSTRACT
A gradient, reversed-phase liquid chromatographic (RP-LC) assay method was developed for the quantitative determination of zolmitriptan, used to treat severe migraine headaches. The developed method is also applicable for the related substances determination in bulk drugs. The chromatographic separation was achieved on a Waters X Terra RP18, 250 mm x 4.6 mm, 5 microm column. The gradient LC method employs solutions A and B as mobile phase. The solution A contains a mixture of phosphate buffer pH 9.85:methanol:acetonitrile (70:20:10, v/v/v) and solution B contains a mixture of phosphate buffer, pH 9.85:acetonitrile (30:70). The flow rate was 1.0 ml/min and the detection wavelength was 225 nm. In the developed HPLC method, the resolution between zolmitriptan and its potential impurities, namely Imp-1, Imp-2 and Imp-3 was found to be greater than 3. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in alkaline medium and oxidative stress conditions. Degradation product formed during base hydrolysis was found to be Imp-3. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.5%. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness.
Subject(s)
Chemistry, Pharmaceutical/methods , Chromatography, Liquid/methods , Drug Industry/methods , Oxazolidinones/analysis , Tryptamines/analysis , Acetonitriles/chemistry , Buffers , Calibration , Chromatography , Chromatography, High Pressure Liquid , Hydrogen-Ion Concentration , Hydrolysis , Models, Chemical , Oxazolidinones/chemistry , Oxygen/chemistry , Pharmaceutical Solutions/analysis , Photolysis , Reproducibility of Results , Sensitivity and Specificity , Serotonin Receptor Agonists/analysis , Serotonin Receptor Agonists/chemistry , Solubility , Tryptamines/chemistryABSTRACT
A new, accurate and reliable chiral HPLC method was developed for the determination of Zolmitriptan, (4S)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl] methyl]-2-oxazolidinone an antimigraine agent and its potential impurities namely (4R)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl] methyl]-2-oxazolidinone [(R)-enantiomer] and (4S)-4-(4-aminobenzyl)-2-oxazolidinone (Imp-1) in pharmaceutical formulations and in bulk drugs. HPLC separation was carried out by normal phase chromatography with a mobile phase composed of hexane:isopropanol:methanol:diethylamine in the ratio (75:10:15:0.1, v/v/v/v) pumped at a flow rate of 1.0 ml/min on a Chiralpak AD-H column. Zolmitriptan and its potential impurities were baseline resolved in the optimized method. The presence of diethylamine in the mobile phase has played a key role in achieving chromatographic resolution between the enantiomers and also in enhancing chromatographic efficiency. The developed method was also found to be selective under exposed conditions UV light and 60 degrees C. The developed method was completely validated and proved to be robust. The values of the limit of detection (LOD) and limit of quantification (LOQ) of (R)-enantiomer and Imp-1 were 100, 250 ng/ml and 30, 1000 ng/ml, respectively, for 10 microl injection volume. The validated method yielded good results regarding selectivity, linearity, precision, accuracy and ruggedness. Zolmitriptan sample solution and mobile phase are found to be stable for at least 24 h. The proposed method was found to be suitable and accurate for the quantitative determination of Zolmitriptan and its impurities namely (R)-enantiomer and Imp-1 in bulk drugs and commercial formulations.
Subject(s)
Drug Contamination , Oxazolidinones/analysis , Chromatography, Liquid/methods , Drug Contamination/prevention & control , Oxazolidinones/chemistry , TryptaminesABSTRACT
An isocratic, reversed-phase liquid chromatographic (RPLC) method was developed for the quantitative determination of Rivastigmine hydrogen tartrate, a cholinesterase inhibitor in bulk drugs and in pharmaceutical dosage forms. The developed method is also applicable for the related substance determination of Rivastigmine hydrogen tartrate in bulk drugs. The chromatographic separation was achieved on a Waters X Terra RP18 (250 mm x 4.6 mm, 5 microm) column using aqueous 0.01 M sodium-1-heptane sulphonate (pH: 3.0 with dilute phosphoric acid)-acetonitrile (72:28, v/v) as a mobile phase. The chromatographic resolution between Rivastigmine and its potential impurity, namely (S)-3-(1-dimethylaminoethyl) phenol (Imp 1) was found to be greater than four. Forced degradation studies were performed for Rivastigmine hydrogen tartrate bulk drug using acid (0.5 N hydrochloric acid), base (0.5 N sodium hydroxide), oxidation (3% hydrogen peroxide), heat (60 degrees C) and UV light (254 nm). No degradation was observed for Rivastigmine hydrogen tartrate except in base hydrolysis and the formed degradation product was found to be Imp 1. The mass balance of Rivastigmine hydrogen tartrate was close to 100 in all the stress conditions. The limit of detection (LOD) and limit of quantification (LOQ) of Imp 1 were found to be 100 and 300 ng/ml, respectively, for 10 microl injection volume. The percentage recovery of Imp 1 in bulk drug sample was ranged from 95.2 to 104.3. The active pharmaceutical ingredient was extracted from its finished dosage form (capsule) using water. The percentage recovery of Rivastigmine hydrogen tartrate was ranged from 99.2 to 101.3 and 98.6 to 101.5 in bulk and pharmaceutical formulation samples, respectively. Rivastigmine hydrogen tartrate sample solution and mobile phase were found to be stable for at least 48 h. The developed method was validated with respect to linearity, accuracy, precision, robustness and forced degradation studies prove the stability indicating power of the method.
