K.V.S.R. Krishna Reddy

Stability-indicating UPLC method for determination of Valsartan and their degradation products in active pharmaceutical ingredient and pharmaceutical dosage forms.

A simple, precise, accurate stability-indicating gradient reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed for quantitative determination of purity of Imatinib Mesylate (IMM) drug substance and drug products in the presence of its process related impurities, and degradation products. The proposed RP-UPLC method utilizes Acquity UPLC BEH 50-mm, 2.1mm and 1.7 μm C-18 column at 30 °C, with a gradient program of 9.0 min at a flow rate of 0.3 mL/min. The compounds of interest were monitored at 237 nm. Resolution for Imatinib and eight related components was found to be greater than 1.5 for any pair of components. The correlation coefficients (r(2)>0.9990) obtained indicate clear correlations between the concentrations and their peak areas for the investigated compounds. RSD obtained for the repeatability and intermediate precision experiments, was less than 5.0%. Accuracy of the method was further ascertained by performing recovery studies through spiking experiments. The drug substance was subjected to hydrolytic, oxidative, photolytic 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 quantitation, linearity, accuracy, precision, ruggedness and robustness. The method is also suitable for the assay determination of IMM in pharmaceutical dosage forms.

A validated CE method for determining dimethylsulfate a carcinogen and chloroacetyl chloride a potential genotoxin at trace levels in drug substances

A simple and rapid capillary zone electrophoretic method was developed for determining dimethyl sulfate a possible human carcinogen and mutagen and chloroacetyl chloride a potential genotoxic agent at trace levels in pharmaceutical drug substances by indirect photometric detection. A systematic screening of various anionic probes was performed to obtain the best separation conditions and sensitivity. High sensitivities with low quantification and detection levels were achieved for dimethylsulfate and chloroacetyl chloride using a background electrolyte (BGE) containing 5 mM pyridine dicarboxylic acid as the probe ion. The method is specific, precise and accurate for the two genotoxins. The optimized method was validated for specificity, precision, linearity, accuracy and stability in solution. Calibration curves were linear (R>0.999) for both dimethylsulfate and chloroacetyl chloride in the range LOQ - 300% of nominal concentrations. The CE method was effectively implemented for estimating dimethylsulfate and chloroacetyl chloride in two different active pharmaceutical ingredients (APIs).

Isolation and characterization of process-related impurities in linezolid.

Two unknown impurities in linezolid bulk drug at levels below 0.1% (ranging from 0.05 to 0.1%) were detected by a simple isocratic reverse phase high performance liquid chromatography (HPLC). These impurities were isolated from crude sample of linezolid using reverse phase preparative HPLC. Based on the spectroscopic data (IR, NMR and MS) the structures of the impurities were characterized as (S)-N-[[-(3-(3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl] acetate(I) and (S)-N-[[-(3-(3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl] chloride(II). The synthesis from an unambiguous route and the formation of impurities was discussed.

Impurity profile study of repaglinide.

Three unknown impurities and a byproduct in repaglinide bulk drug at levels below 0.1% (ranging from 0.05 to 0.1%) were detected by a simple isocratic reversed-phase high performance liquid chromatography (HPLC) method. These impurities were isolated from crude sample of repaglinide using reversed-phase preparative high performance liquid chromatography. Based on the spectroscopic data (IR, NMR and MS) the structures of these impurities (I, II and IV) and byproduct (III) were characterised as 4-carboxymethyl-2-ethoxy-benzoic acid (I), 4-cyclohexylaminocarbamoylmethyl-2-ethoxy-benzoic acid (II), 1-cyclohexyl-3-[3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl]-urea (IV) and 1,3-dicyclohexyl urea (III), respectively. Their synthesis and formation is discussed.

Impurity profile study of loratadine

Three unknown impurities in loratadine bulk drug at levels below 0.1% (ranging from 0.05 to 0.1%) were detected by a simple isocratic reversed-phase high performance liquid chromatography (HPLC). These impurities were isolated from mother liquor sample of loratadine using reversed-phase preparative HPLC. Based on the spectral data (IR, NMR and MS) the structures of these impurities were characterized as 11-(N-carboethoxy-4-piperidylidene)-6,11-dihydro-5H-benzo(5,6) cyclopenta(1,2-b)-pyridine (I), 8-bromo-11-(N-carboethoxy-4-piperidylidene)-6,11-dihydro-5H-benzo(5,6) cyclopenta (1,2-b)-pyridine (II) and 8-chloro-11-(N-carboethoxy-4-piperidylidene)-5H-benzo(5,6) cyclopenta (1,2-b)-pyridine (III). The synthesis of these impurities was discussed.

Isolation and characterisation of process-related impurities in rofecoxib.

Two unknown impurities in rofecoxib bulk drug at levels below 0.1% were detected by a simple isocratic reverse phase high performance liquid chromatography (HPLC). These impurities were isolated from crude sample of rofecoxib using reverse phase preparative HPLC. (1)H, (13)C and Mass spectroscopic investigations revealed the structures of the impurities as 4-[4-(methylsulphonyl)phenyl]-3-phenyl-5-hydroxyfuran-2-one (I) and 4-[4-(methylsulphonyl)phenyl]-3-phenyl-2,5-furandione (II), respectively. These structures were further confirmed by prepared synthetic standards of the impurities. The tentative mechanism for the formation of these impurities was discussed.

Development and validation of a stability indicating HPLC method for simultaneous determination of four novel fluoroquinolone dimers as potential antibacterial agents.

A series of novel 6-fluoro1,4-dihydro-4-oxo-3-quinoline carboxylic acid dimers were synthesized as potential antibacterial agents from commercially available substituted fluorobenzoic acids. A stability indicating HPLC method was developed to determine these novel fluoroquinolone dimers using a systematic method development approach. Samples were subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation; and analyzed to demonstrate the specificity and stability indicating ability of the developed method. The precision for all four fluoroquinolone dimers was within 2.0% RSD. Calibration curves were linear (LOQ, 150%), with regression coefficients >0.99 for all dimers. The method was conveniently applied for determining purity and assay of these four novel fluoroquinolone dimers.

Porcine liver esterase catalyzed kinetic resolution of baylis-hillman (B-H) adducts

Abstract Esterase from porcine liver smoothly resolves varieties of racemic 2-methylene-3-substituted-3-hydroxypropanoates (B-H adducts) to obtain the corresponding unreacted esters in very good to excellent ee (94 to >99%, seven examples) and hydrolyzed acids in good ee (58–75%). Substitution in B-H adducts, chosen for resolution, are funtionalized phenyl, thiophen-3-yl, cinnamyl, and alkyl groups. †DRL Pub. No. 232. Dedicated to Dr. A. Venkateswarlu on the occasion of his 63rd birth anniversary

LC method for the quantitative determination of oxaprozin and its impurities in the bulk drug

A reversed phase linear gradient liquid chromatographic method was developed for the separation and quantitative determination of the seven known process related impurities and one degraded product of oxaprozin in the bulk drug material. An Inertsil-ODS 3V (150 x 4.6 mm), 5 microm column was operated with a phosphate buffer acetonitrile gradient. Detection was carried out on a UV detector at 254 nm. This method has been proved to be accurate and sensitive. The limits of detection (LOD) and limits of quantification (LOQ) of impurities were in the order of 5-60 ng and 16-200 ng, respectively. In addition to its ruggedness and robustness, this method offers identification of all eight impurities in a single run.

Stabilization of Clay at Sunnam Cheruvu Area in Nadergul, Hyderabad Using Organic Waste

Clay soils inherit certain problems due to its properties such as plasticity, volume change, low strength, etc. To overcome these problems an attempt has been made in the present study to determine the utility of organic waste in stabilization of clay which has been obtained from Sunnam Cheruvu area of Nadergul, Hyderabad. Organic wastes have been considered due to their economical and environmental advantage. Ash of sugarcane pulp, wood, and coconut shell have been considered to investigate their potential in stabilizing the clay soil in pursuit of obtaining a cheaper and effective stabilizer. Laboratory experimentation was done to evaluate the differential free swell and unconfined compressive strength (UCC) for various percentages of ash contents. Curing of stabilized soil samples for 7 and 28 days were considered. Stabilization also required addition of lime to control swell. The results show that the swell and strength properties of samples were improved with the addition of various ash contents and also with curing period. Therefore it is concluded that sugar cane pulp ash, wood ash and coconut shell ash have a good potential in improving the properties of clay soil.