ABSTRACT
A rapid, specific and reliable isocratic LC-MS/MS method has been developed and validated for the identification and characterization of stressed degradation products of Zofenopril. Zofenopril, an anti-hypertensive drug, was subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolysis and thermal stress, as per ICH-specified conditions. The drug showed extensive degradation under oxidative and base hydrolysis stress conditions. However, it was stable to thermal, acid, neutral and photolysis stress conditions. A total of 6 degradation products were observed and the chromatographic separation of the drug and its degradation products were achieved on Phenomenex (Luna) C18 (250mm×4.6mm, i.d., 5µm) column using 20mM ammonium acetate: acetonitrile (50:50, v/v) as a mobile phase. The degradation products were characterized by LC-MS/MS and its fragmentation pathways were proposed. The LC-MS method was validated with respect to specificity, linearity, accuracy and precision. No previous reports were found in the literature regarding the degradation behavior of zofenopril.
Subject(s)
Captopril/analogs & derivatives , Antihypertensive Agents/analysis , Antihypertensive Agents/chemistry , Captopril/analysis , Captopril/chemistry , Chromatography, High Pressure Liquid , Chromatography, Liquid , Drug Stability , Hydrolysis , Limit of Detection , Oxidative Stress , Oxygen/chemistry , Photolysis , Reproducibility of Results , Tandem Mass Spectrometry , TemperatureABSTRACT
A selective RP-HPLC method for separation and determination of darunavir from its process related substances has been developed and validated. The separation was accomplished on a Hiber, LiChrospher 60, RP-select B, C8 (250 mm × 4.6 mm, 5 µm) column connected to a photo diode array detector (PDA) using 10 mM phosphate buffer with 0.1% of triethylamine (pH: 4.0 adjusted with orthophosphoric acid)/acetonitrile as a mobile phase under gradient elution. Two unknown impurities of darunavir were isolated and characterized by ¹H, ¹³C, 2D-NMR and mass spectrometry. The method was validated in terms of accuracy, precision, linearity, robustness, LOD and LOQ.
Subject(s)
Drug Contamination , HIV Protease Inhibitors/chemistry , Sulfonamides/chemistry , Chromatography, High Pressure Liquid , Chromatography, Reverse-Phase , Darunavir , Drug Stability , Electrochemical Techniques , Guidelines as Topic , HIV Protease Inhibitors/analysis , India , Limit of Detection , Magnetic Resonance Spectroscopy , Molecular Structure , Molecular Weight , Quality Control , Reproducibility of Results , Spectrometry, Mass, Electrospray Ionization , Sulfonamides/analysisABSTRACT
The use of 3-methylimidazolium cation-based ionic liquids (ILs) was evaluated as mobile phase additives for separation of antiretroviral drugs on a monolithic column by RP-HPLC. Separation of eight commonly used antiretroviral drugs was achieved on a Chromolith Flash, RP-18e column (25 × 4.6 mm, porous material) using water (pH 4.0 adjusted with acetic acid)/methanol v/v as a mobile phase containing ILs in a gradient elution mode. The effects of concentrations of ILs on retention, resolution and peak shape were studied and a regression equation correlating the interactions between stationary phase and the ILs was established. The retention of all the drugs was decreased notably by using 1-butyl-3-methylimidazolium tetrafluoroborate, while 1-ethyl-3-methylimidazolium methylsulfate reduced gradient drift drastically when compared to triethylamine.
Subject(s)
Antiviral Agents/isolation & purification , Chromatography, Reverse-Phase/methods , Adsorption , Antiviral Agents/analysis , Chromatography, Reverse-Phase/instrumentation , Ionic Liquids/chemistryABSTRACT
Armodafinil is a unique psychostimulant recently approved by the US Food and Drug Administration for the treatment of narcolepsy. The chromatographic resolution of its chiral intermediates including related substances in the total synthesis of armodafinil was studied on polysaccharide-based stationary phases, viz. cellulose tris-(3,5-dimethylphenylcarbamate) (Chiralcel OD-H) and amylose tris-(3,5-dimethylphenylcarbamate) (Chiralpak AD-H) by HPLC. The effects of 1-propanol, 2-propanol, ethanol, and trifluoroacetic acid added to the mobile phase and of column temperature on resolution were studied. A good separation was achieved on cellulose-based Chiralcel OD-H column compared to amylose-based Chiralpak AD-H. The effects of structural features of the solutes and solvents on discrimination between the enantiomers were examined. Baseline separation with R(s) >1.38 was obtained using a mobile phase containing n-hexane-ethanol-TFA (75:25:0.15 v/v/v). Detection was carried out at 225 nm with photodiode array detector while identification of enantiomers was accomplished by a polarimetric detector connected in series. The method was found to be suitable not only for process development of armodafinil but also for determination of the enantiomeric purity of bulk drugs and pharmaceuticals.
