Entity

Time filter

Source Type


Srinivas N.R.,Vanthys Pharmaceutical Development Pvt Ltd | Mullangi R.,Jubilant Biosys Ltd.
Biomedical Chromatography | Year: 2011

Although plasma/serum is the preferred matrix for the characterization of pharmacokinetic parameters, recent years have witnessed the emergence of bile matrix as another tool for refining the pharmacokinetic disposition of drug(s) and the associated metabolite(s). The biliary excretion mechanism represents an important path for drug elimination through feces. Also, there are numerous examples in which bile samples have been shown to concentrate both drug and its metabolite(s) in a much higher proportion as compared with the circulating blood levels and may act as a reservoir for the re-entry of the drug and its metabolite(s) to the systemic circulation once the bile gets drained into the small intestine.Firstly, the review provides a comprehensive overview of various analytical methods that have been adopted for bile sample analysis with a description of extraction steps, chromatography and validation protocol. Secondly, it provides a discussion on bioanalytical related strategies including bile sample collection requirements. Thirdly, a brief discussion on fit-for-use method strategy is also presented to enable an optimum allotment of resources for bile related analysis; and finally, the use of bile matrix in several mechanistic studies to probe efflux mechanisms and/or drug-drug interaction potential has been presented with relevant case studies. © 2010 John Wiley & Sons, Ltd. Source


Sharma S.,Clinsys Clinical Research Ltd | Dubey N.K.,Clinsys Clinical Research Ltd | Dasgupta A.K.,Clinsys Clinical Research Ltd | Sahu M.,Vanthys Pharmaceutical Development Pvt Ltd | And 3 more authors.
Biomedical Chromatography | Year: 2012

A highly sensitive, rapid assay method has been developed and validated for the estimation of JI-101 in human plasma and urine using LC-MS/MS-ESI in the positive-ion mode. The assay procedure involves extraction of JI-101 and alfuzosin (internal standard, IS) from human plasma/urine with a solid-phase extraction process. Chromatographic resolution was achieved on two Zorbax SB-C18 columns connected in series with a PEEK coupler using an isocratic mobile phase comprising acetonitrile-0.1% formic acid in water (70:30, v/v). The total run time was 2.0min. The MS/MS ion transitions monitored were 466.20→265.10 for JI-101 and 390.40→156.10 for IS. The method was subjected to rigorous validation procedures to cover the following: selectivity, sensitivity, matrix effect, recovery, precision, accuracy, stability and dilution effect. In both matrices the lower limit of quantitation was 10.0ng/mL and the linearity range extended from ~10.0 to 1508ng/mL in plasma or urine. The intra- and inter-day precisions were in the ranges 1.57-14.5 and 6.02-12.4% in plasma and 0.97-15.7 and 8.66-10.2% in urine. This method has been successfully applied for the characterization of JI-101 pharmacokinetics in cancer patients. © 2011 John Wiley & Sons, Ltd. Source


Mullangi R.,Jubilant Biosys Ltd. | Srinivas N.R.,Vanthys Pharmaceutical Development Pvt Ltd
Biomedical Chromatography | Year: 2011

Niacin (nicotinic acid), although an old drug, has seen a sudden surge in popularity for treatment of lipid disorders and other associated clinical conditions for the prevention of cardiovascular risk. Also, there has been considerable interest in clarifying the role of metabolic pathways of niacin in explaining the tolerability/adverse affect profile of the agent. Hence, it has become very important to quantify/monitor the levels of niacin and its metabolites in various clinical studies. This review describes the recent trends in the bioanalysis of niacin and its metabolites, where HPLC and LC-MS/MS assays have been successfully employed to measure the drug levels in various biological matrices arising from preclinical and clinical studies. In addition, this review encompass various considerations such as internal standard selection, extraction schemes, matrix effect, selectivity evaluation and optimization of mass spectral conditions to enable the development of sound bioanalytical methods for niacin alone or niacin along with its metabolites. Recent updates pertaining to the clinical pharmacology of niacin and ongoing debate for the clarification of adverse effects are also provided. Overall LC-MS/MS methods have proven to be choice of bioanalytical method for the quantification of niacin alone or with its metabolites in both preclinical and clinical studies. © 2010 John Wiley & Sons, Ltd. Source


Srinivas N.R.,Vanthys Pharmaceutical Development Pvt Ltd
European Journal of Drug Metabolism and Pharmacokinetics | Year: 2011

The concept of prodrugs has been successfully executed for life cycle management options of several approved drugs and drugs in development. In addition to imparting ideal biopharmaceutical properties, such as solubility, permeability and lipophilicity, some prodrug concepts have also enabled site-specific drug delivery, prolonged the duration of therapeutic effect and improved therapeutic index. The strategic inclusion of prodrug concept during drug discovery and early development process brings in some unique challenges. The communication provides balanced perspectives on the rational use and challenges of prodrug concept during the drug discovery and development process. © Springer-Verlag France 2011. Source


Gurav S.D.,Jubilant Biosys Ltd. | Gilibili R.R.,Jubilant Biosys Ltd. | Jeniffer S.,Jubilant Biosys Ltd. | Giri S.,Jubilant Biosys Ltd. | And 2 more authors.
Biomedical Chromatography | Year: 2011

A highly sensitive, rapid assay method has been developed and validated for the estimation of JI-101 in rat plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive-ion mode. The assay procedure involves extraction of JI-101 and phenacetin (internal standard, IS) from rat plasma with a solid-phase extraction process. Chromatographic separation was achieved using a binary gradient using mobile phase A (acetonitrile) and B (0.2% formic acid in water) at a flow rate of 0.30mL/min on a Prodigy ODS column with a total run time of 4.0min. The MS/MS ion transitions monitored were 466.1 → 265 for JI-101 and 180.1 → 110.1 for IS. Method validation and sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 5.03ng/mL and the linearity range extended from 5.03 to 2014ng/mL. The intra-day and inter-day precisions were in the ranges of 1.17-19.6 and 3.09-10.4%, respectively. This method has been applied to a pharmacokinetic study of JI-101 in rats. © 2010 John Wiley & Sons, Ltd. Source

Discover hidden collaborations