Vanthys Pharmaceutical Development Pvt Ltd

Bangalore, India

Vanthys Pharmaceutical Development Pvt Ltd

Bangalore, India
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Srinivas N.R.,Vanthys Pharmaceutical Development Pvt. Ltd.
Asian Journal of Pharmaceutics | Year: 2011

Bioavailability (BA)/ bioequivalence (BE) studies are the cornerstone for the approval of generic drugs. While BA/BE assessment involving the pharmacokinetic data of the parent compound has been routinely performed, the introduction of the assessment of metabolite(s) data, alone or in addition to parent compound, has also emerged. In this context, the assessment of BA/BE of metabolite(s) may pose additional complexities and challenges, if the metabolic pathway is under the influence of a polymorphic enzyme. This communication provides brief perspectives on the challenges and study design considerations for the assessment of polymorphic metabolite in BA/BE studies.


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.


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

The intravenous pharmacokinetics data of ketorolac in mice, rats, rabbits, dogs and monkeys were assembled fromliterature. The relationship between the main pharmacokinetic parameters [viz., volume of distribution (Vd) and clearance (CL)] and body weight was studied across five mammalian species, using double-logarithmic plots to predict the human pharmacokinetic parameters of CL and Vd using simple allometry or with correction factors [maximum life span potential (MLP), brain weight, CF1 (bile flow/liver weight) and CF2 (bile flow/body weight)]. The metabolism pattern, biotransformation pathways and the predominant urinary excretion of parent and the formed metabolites of ketorolac were found to be similar amongst mice, rats, rabbits, dogs, monkeys and humans, facilitating the scaling process. The human parameter value for Vd was predicted by simple allometric equation: 0.2481W1.0549 (r 2 = 0.9217). The predicted Vd value (21.92 L) is close to the reported value (17.5 L), whereas the CL was predicted by simple allometric approach or with standard correction factors viz., MLP, brain weight, CF1 and CF2. Best proximity CL value was obtained with MLP having allometric equation: 0.7126W1.3264 (r2 = 0.9640). The outcome of this exercise suggests that allometric scaling with suitable correction factors could potentially be used to predict the human pharmacokinetic parameters of drugs belonging to nonsteroidal anti-inflammatory drugs retrospectively. © Springer-Verlag France 2011.


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.


Gurav S.D.,Jubilant Biosys Ltd | Jeniffer S.,Jubilant Biosys Ltd | Punde R.,Jubilant Biosys Ltd | Gilibili R.R.,Jubilant Biosys Ltd | And 3 more authors.
Biomedical Chromatography | Year: 2012

A general practice in bioanalysis is that, whatever the biological matrix the analyte is being quantified in, the validation is performed in the same matrix as per regulatory guidelines. In this paper, we are presenting the applicability of a validated LC-MS/MS method in rat plasma for JI-101, to estimate the concentrations of JI-101 in various tissues that were harvested in a rat tissue distribution study. A simple protein precipitation technique was used to extract JI-101 and internal standard from the tissue homogenates. The recovery of JI-101 in all the matrices was found to be >70%. 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 internal standard. The linearity range was 5.02-4017ng/mL. The JI-101 levels were quantifiable in the various tissue samples harvested in this study. Therefore, the use of a previously validated JI-101 assay in plasma circumvented the tedious process of method development/validation in various tissue matrices. © 2011 John Wiley & Sons, Ltd.


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.


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.


Mullangi R.,Jubilant Biosys Ltd | Sharma K.,Jubilant Biosys Ltd | Srinivas N.R.,Vanthys Pharmaceutical Development Pvt Ltd
Biomedical Chromatography | Year: 2012

Aspirin, the most widely used drug in the world, has been known to mankind for over a century. It is not only the pharmacologically active entity, but is also biotransformed into a major metabolite, i.e. salicylic acid, which also exhibits similar pharmacologic/pharmacodynamic properties. Hence it is necessary to quantitate aspirin along with its metabolite(s) in various biological matrices accurately and precisely to correlate with pharmacological/pharmacodynamic activity. This paper provides a comprehensive overview of various bioanalytical methods (HPLC and LC-MS/MS) that have been reported for direct quantitation of aspirin along with its metabolite(s). The review also provides general information on sample collection, sample processing, internal standard selection, conditions for chromatographic separation, succinct validation data and applicable conclusions for reported assays in a structured manner. © 2012 John Wiley & Sons, Ltd.


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.


PubMed | Vanthys Pharmaceutical Development Pvt Ltd
Type: Journal Article | Journal: Biomedical chromatography : BMC | 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.

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