The Expanding Role of HPLC in Drug Discovery

Kassel, Daniel B.

doi:10.1002/9780470087954.ch11

Cited by 2 publications

(3 citation statements)

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“…As previously described, purity was assessed by comparison of the detector response to the metabolites in the incubation matrix with the response to a blank incubation matrix at the same elution time (Figures 4B,C ) (Espina et al, 2009 ; Walker et al, 2011 ). The assessment by total ion chromatogram (TIC) delivered a purity of 93% for the RXT metabolites contained in that fraction, which is in line with the general purity target for library compounds for activity screening (Kassel, 2007 ). The identification of these metabolites was achieved by comparative fragment ion interpretation with the commercial reference substance of parent drug (RXT, chemically designated as ( E )-ERY-9-[O-[(2-methoxyethoxy)methyl]oxime]) and previously results from other investigators using LC-MS and nuclear magnetic resonance (NMR) (Zhong et al, 2000 ).…”

Section: Resultsmentioning

confidence: 70%

Exploring the Role of CYP3A4 Mediated Drug Metabolism in the Pharmacological Modulation of Nitric Oxide Production

et al. 2017

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Nitric-oxide synthase, the enzyme responsible for mammalian nitric oxide generation, and cytochrome P450, the major enzymes involved in drug metabolism, share striking similarities. Therefore, it makes sense that cytochrome P450 drug mediated biotransformations might play an important role in the pharmacological modulation of nitric oxide synthase. In this work, we have undertaken an integrated in vitro assessment of the hepatic metabolism and nitric oxide modulation of previously described dual inhibitors (imidazoles and macrolides) of these enzymes in order assess the implication of CYP450 activities over production of nitric oxide. In vitro systems based in human liver microsomes and activated mouse macrophages were developed for these purposes. Additionally in vitro production the hepatic metabolites of dual inhibitor, roxithromycin, was investigated achieving the identification and isolation of main hepatic biotransformation products. Our results suggested that for some macrolide compounds, the cytochrome P450 3A4 derived drug metabolites have an important effect on nitric oxide production and might critically contribute to the pharmacological immunomodulatory activity observed.

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Section: Resultsmentioning

confidence: 70%

Exploring the Role of CYP3A4 Mediated Drug Metabolism in the Pharmacological Modulation of Nitric Oxide Production

et al. 2017

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“…An evaluation of the chemical stability of the Gemini and XBridge stationary phases was also performed. In our experience over several years, the tri-functionally bonded C18 ligand of the XBridge BEH C18 sorbent, which can be used in the entire range of mobile phase pH (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and exhibits ultra-low column bleed, showed a good stability during the evaluated time, allowing more than 2000 analyses at high pH and elevated temperature without any loss in efficiency. In contrast, in our hands the Gemini column showed lower stability at low pH, giving a typical life time of 400-700 injections.…”

Section: Defining Chromatographic Methods For Purity Assessment: Columentioning

confidence: 96%

“…However purity requirements and analytical procedures differ according to the drug discovery stage from chemical synthesis to compound selection for development (2,3). Whereas in later stages of pharmaceutical development, individually validated methods for each active pharmaceutical ingredient (API) are necessary and required by regulators, such an approach is not practical in earlier stages of discovery and generic methods applicable to a range of compounds must be used to deliver acceptable analysis rates.…”

Section: Introductionmentioning

confidence: 99%