ABSTRACT
A new rapid stability-indicating reversed-phase UPLC method was developed and validated for the determination of Bromfenac sodium and its impurities in Bromfenac ophthalmic solution. During literature search, only a few publications were found about Bromfenac sodium. There is no official monograph in the pharmacopoeias about Bromfenac sodium. Chromatographic separation has been achieved on a polar-embedded Waters Acquity BEH Shield RP18 (100 mm × 2.1 mm, 1.7 µm) column under gradient elution by using a binary mixture of potassium dihydrogen phosphate (0.01 M, pH 3.3) and acetonitrile (ACN) at a flow rate of 0.5 mL/min. Chromatogram was monitored at 265 nm using a photodiode array detector (PDA). The drug and its related impurities are eluted within 13 min. Resolution of Bromfenac sodium and all eight potential impurities have been achieved greater than 4.0 for all pairs of compounds. To prove the stability-indicating power of the method, the drug was subjected to hydrolytic (acid, alkaline and water), oxidative, photolytic and thermal stress, and the major degradation products were identified based on LC-MS analysis. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, precision, accuracy and robustness.
ABSTRACT
A novel, simple, sensitive, selective and reproducible stability-indicating high performance liquid chromatographic method was developed for the quantitative determination of degradation products and process-related impurities of ketoprofen (KET) and omeprazole (OMZ) in combined oral solid dosage form. Chromatographic separation was achieved on a Phenomenex Luna C18 (2) column (150 × 4.6 mm, 5 µm) under gradient elution by using a binary mixture of potassium dihydrogen phosphate buffer and acetonitrile at a flow rate of 0.8 mL/min. Chromatogram was monitored at 233 nm for KET impurities and at 305 nm for OMZ impurities using a dual wavelength UV detector. Resolution for KET and OMZ and 14 impurities was found to be >1.5 for any pair of components. Typical retention behaviors of impurities at various pH values were depicted graphically. To prove the stability-indicating power of the method, the drug product was subjected to hydrolytic, oxidative, photolytic, humidity and thermal stress conditions as per ICH. The developed method was validated according to the current ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness and robustness.
Subject(s)
Capsules/chemistry , Chromatography, High Pressure Liquid/methods , Chromatography, Reverse-Phase/methods , Ketoprofen/analysis , Omeprazole/analysis , Drug Combinations , Reference StandardsABSTRACT
A simple, inexpensive and rapid liquid chromatography (LC) method has been developed for the quantitative determination of Lomustine, an chemotherapy drug. Degradation studies were performed on the bulk drug by heating to 60 °C, exposure to UV light at an energy of 200 Wh/m(2)and to visible light at an illumination of not less than 1.2 million lux hours, acid (0.1N hydrochloric acid), base (0.1N sodium hydroxide) aqueous hydrolysis and oxidation with 6.0% (v/v) hydrogen peroxide. Good resolution between the peaks corresponding to impurities produced during synthesis, degradation products and the analyte was achieved on a Symmetry C 8 LC column using a mobile phase consisting of a mixture of aqueous potassium dihydrogen phosphate and acetonitrile. The degradation samples were assayed against the reference standard of Lomustine and the mass balance in each case was close to 99.9%. Validation of the method was carried out as per International Conference on Harmonization (ICH) requirements.
Subject(s)
Chemistry, Pharmaceutical/methods , Chromatography, Liquid/methods , Lomustine/analysis , Acetonitriles/chemistry , Chemistry Techniques, Analytical , Chromatography/methods , Drug Stability , Hydrogen Peroxide/chemistry , Hydrolysis , Lomustine/chemistry , Models, Chemical , Reproducibility of Results , Temperature , Ultraviolet RaysABSTRACT
To demonstrate the applicability of thermogravimetric analyzer as a tool for the quantification of pantaprazole sodium monohydrate in sesquihydrate, studies have been conducted. Thermal analysis (DSC, TGA) crystallographic (PXRD) and spectroscopic techniques (FT-IR) were used for the characterization of the polymorphs. Thermogravimetric analysis (TGA) analysis was explored by high-resolution dynamic (Hi-Res-dynamic) and high-resolution modulated (Hi-Res-modulated) test procedures to quantify the hydrate polymorphic mixtures. The two polymorphic forms exhibited significant differences and good resolution in the second derivative thermogram generated by Hi-Res-modulated test procedure. Thus, the TGA with Hi-Res-modulated test procedure was considered for the quantification of monohydrate in sesquihydrate. The calibration plot was constructed from the known mixtures of two polymorphs by plotting the peak area of the second derivative thermogram against the weight percent of monohydrate. Using this novel approach, 1 wt% limit of detection (LOD) was achieved. The polymorphic purity results, obtained by TGA in Hi-Res-modulated test procedure were found to be in good agreement with the results predicted by FT-IR and was comparable with the actual values of the known polymorphic mixtures. The Hi-Res-modulated TGA technique is very simple and easy to perform the analysis.
