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Bangalore, India

Mullangi R.,Jubilant Biosys | Srinivas N.R.,Suramus Biopharm
Biomedical Chromatography | Year: 2013

Clinical investigations of choleteryl ester transfer protein (CETP) inhibitors are still underway owing to its promise of reducing risk factors in patients with cardiovascular disease. Although several CETP inhibitors have reached late phase clinical testing, there is a paucity of publications that describe the determination of various CETP inhibitors in human and/or animal matrices. An attempt is made in this review to collate bioanalytical information on three CETP inhibitors (anacetrapib, dalcetrapib and torcetrapib) and its metabolites, where data were available and reported. As elaborated in the review, owing to numerous structural issues coupled with chromatography/detection challenges indigenous to the class, a wide array of analytical tools, detection systems, interesting process manipulations and separation nuances have been utilized for the quantitative analysis of CETP inhibitors and applicable metabolites. Copyright © 2013 John Wiley & Sons, Ltd. © 2013 John Wiley & Sons, Ltd.


Baicalin was extensively researched for utility in a number of therapeutic areas owing to its anti-inflammatory, anti-oxidant, anti-bacterial, and anti-cancer properties. A number of preclinical studies, in vitro work, and mechanistic studies were performed to understand the absorption, distribution, metabolism, and excretion profiles of baicalin. The absorption of baicalin involved several complexities: the restriction to two distant sites; the conversion of baicalin to baicalein; the possible role of transporter(s); and enhanced absorption due to breakdown of conjugates by beta-glucuronidase. Limited distribution data suggest that baicalin reached several sites such as the brain, eye lens, thymus, etc. Hepatobiliary recycling also served as a distribution phase for sustained delivery of baicalin. Metabolism data suggest the rapid conversion of baicalin to baicalein, which was extensively subjected to Phase 2 metabolism, conjugates baicalein glucuronide/sulfate have been identified. Limited excretion data suggest involvement of renal and faecal routesglucuronide and sulfate conjugates were excreted in urine and faeces (via biliary excretion). The published data on baicalin suggest imminent challenges for developing baicalin and/or during co-administration with other agents. These challenges are absorption related (transporter or changes in the microenvironment), metabolism related (CYP2B6 induction and/or CYP2E1 inhibition), and excretion/efflux related (competitive biliary pathway and/or OATP1B1 transport).


D'Souza H.J.B.,Lotus Labs. Pvt. Ltd. | Pai B.,Lotus Labs. Pvt. Ltd. | Kumar A.,Lotus Labs. Pvt. Ltd. | Shekar R.,Lotus Labs. Pvt. Ltd. | And 2 more authors.
Biomedical Chromatography | Year: 2010

While the practice of using a smaller number of non-zero standards (typically seven to eight) has not been entertained in routine bioanalytical work, it is important to innovate and be pragmatic about minimizing the number of calibration standards to promote cost-eff ective and speedy assessment. In this exercise, two important compounds, omeprazole and clopidogrel carboxylic acid, were considered. Additionally, both analytes off ered a 1000-fold calibration curve range with eight non-zero standards to permit a systematic evaluation. Accordingly various scenarios of post-hoc analysis of the calibration data were formulated which included step-wise reduction of the number of calibration standards from a maximum of n = 8 to a minimum of n = 3. In all the scenarios evaluated in this exercise, a calibration curve was reconstructed and both quality control samples and in vivo pharmacokinetics were calculated in each instance. Based on the data generated in this exercise, a minimum of three non-zero calibration standards were adequate to predict the quality control samples with the predefined accuracy and precision estimates for both omeprazole and clopidogrel carboxylic acid. Additionally, the in vivo pharmacokinetic characterization of the chosen compounds was not hampered by the reduction of calibration standards (from n = 8 to n = 3). Hence, consideration for reducing number of calibration standards in bioanalytical work may provide a viable alternative in several situations such as formulation screening strategies, routine therapeutic drug monitoring and sparse sample analyses. Copyright © 2009 John Wiley & Sons, Ltd.


Srinivas N.R.,Suramus Biopharm
European Journal of Drug Metabolism and Pharmacokinetics | Year: 2013

The area of fruit juice-drug interaction has received wide attention with numerous scientific and clinical investigations performed and reported for scores of drugs metabolized by CYP3A4/CYP2C9. While grapefruit juice has been extensively studied with respect to its drug-drug interaction potential, numerous other fruit juices such as cranberry juice, orange juice, grape juice, pineapple juice and pomegranate juice have also been investigated for its potential to show drug-drug interaction of any clinical relevance. This review focuses on establishing any relevance for clinical drug-drug interaction potential with pomegranate juice, which has been shown to produce therapeutic benefits over a wide range of disease areas. The review collates and evaluates relevant published in vitro, preclinical and clinical evidence of the potential of pomegranate juice to be a perpetrator in drug-drug interactions mediated by CYP3A4 and CYP2C9. In vitro and animal pharmacokinetic data support the possibility of CYP3A4/CYP2C9 inhibition by pomegranate juice; however, the human relevance for drug-drug interaction was not established based on the limited case studies. © 2013 Springer-Verlag France.


Manjunath S.J.,Lotus Labs. Pvt. Ltd. | Kamath N.,Lotus Labs. Pvt. Ltd. | Shekar A.K.R.,Lotus Labs. Pvt. Ltd. | Srinivas N.R.,Suramus Biopharm | Kristjansson F.,Lotus Labs. Pvt. Ltd.
Biomedical Chromatography | Year: 2010

Sensitivity enhancement via summation of multiple MRM transition pairs is gaining popularity in tandem mass spectrometric assays. Numerous validation experiments describing the assays for two model substrates, clopidogrel and ramiprilat, were performed. The quantitation of clopidogrel was achieved by the summation of transition pairs m/z 322.2 to m/z 212.0 and m/z 322.2 to m/z 184.0, while that of ramiprilat was achieved by the summation of transition pairs m/z 389.2 to m/z 206.1 and m/z 389.2 to m/z156.1. The use of summation approach achieved sensitivities of >2 fold for both compounds as compared with the reported single MRM transition pair assays. The validation experiments addressed some important assay development issues, such as: (a) lack of impact of matrix effect; (b) unequivocal verification of the percentage contribution of each MRM transition pair towards sensitivity; (c) sensitivity enhancement factor achieved by summation approach of MRM transition pairs; and (d) accurate prediction of quality control samples using summation approach vs a single MRM transition pair. In summary, the appropriateness of using two MRM transition pairs for quantitation was demonstrated for both clopidogrel and ramiprilat. Additionally, pharmacokinetic application of the MRM transition pair assays using a summation approach was established for the two compounds. Copyright © 2009 John Wiley & Sons, Ltd.

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