V.Ranga Reddy

Development and Validation of a Simple, Sensitive, Selective and Stability-Indicating RP-UPLC Method for the Quantitative Determination of Ritonavir and Its Related Compounds

A simple, sensitive, selective and reproducible stability-indicating ultra-performance liquid chromatographic method was developed for the quantitative determination of degradation products and process-related impurities of Ritonavir in a pharmaceutical dosage form. Chromatographic separation was achieved on a polar embedded Waters Acquity BEH Shield RP18 (100 × 2.1 mm, 1.7 μm) column thermostated at 50°C under gradient elution by using a binary mixture of potassium dihydrogen phosphate (0.01 M, pH 3.5) and acetonitrile at a flow rate of 0.5 mL/min. Chromatogram was monitored at 240 nm using a photodiode array detector. The drug and its related impurities are eluted within 20 min. To prove the stability-indicating power of the method, the drug was subjected to hydrolytic (acid, alkaline and water), oxidative, photolytic and thermal stress conditions. The unknown degradants were identified by the LC-MS-MS method, which revealed protonated molecular ion peaks [M + H](+) at m/z 551.40 for hydrolytic degradants, and m/z 737.60 and m/z 753.40 for photolytic degradants. A plausible mechanism for the formation of degradation and process impurities was proposed. The performance of the method was validated according to the International Conference on Harmonization guidelines.

A stability-indicating liquid chromatographic method for Lomustine

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.

STABILITY-INDICATING UPLC METHOD FOR DETERMINATION OF RAMELTEON AND THEIR DEGRADATION PRODUCTS IN ACTIVE PHARMACEUTICAL INGREDIENTS

A novel stability-indicating mass compatible gradient reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed for the quantitative determination of purity of Ramelteon drug substance samples in the presence of its impurities and degradation products. The method was developed using Waters Acquity UPLC BEH SHIELD RP18 (100 mm × 2.1 mm, 1.7 µm) column with mobile phase containing a gradient mixture of solvents A and B. The eluted compounds were monitored at 230 nm, the run time was 10 min within which Ramelteon and its four impurities were well separated. Ramelteon was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal, and photolytic degradation. Ramelteon was found to degrade significantly in acidic and slightly in oxidative stress conditions and stable in base, hydrolytic, and photolytic degradation conditions. The degradation products were well resolved from main peak and its impurities, proving the stability-indicating power of the method. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision, and robustness.

Development and Validation of a Novel Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Related Substances of Ketoprofen and Omeprazole in Combined Capsule Dosage Form

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.

LIQUID CHROMATOGRAPHIC METHOD FOR THE SEPARATION OF ANOMERS OF MIGLITOL

A simple, inexpensive, and rapid liquid chromatography (LC) method has been developed for the quantitative determination of anomers of Miglitol, an oral anti diabetic drug. Degradation studies were performed on the bulk drug by heating to 60°C, exposure to UV light at an energy of 200 Watt hours/m2and to Visible light at an illumination of not less than 1.2 million lux hours, acid (0.1 N hydrochloric acid), base (0.1 N sodium hydroxide) aqueous hydrolysis, and oxidation with 6.0% v/v hydrogen peroxide. Good resolution between the peaks corresponding to anomeric impurities, degradation products, and the analyte was achieved on a Waters amino column using a mobile phase consisting of a mixture of aqueous ammonium dihydrogen phosphate and acetonitrile. The degradation samples were assayed against the reference standard of Miglitol and the mass balance in each case was close to 99.0%. Validation of the method was carried out as per International Conference on Harmonization (ICH) requirements.