Research Topics
| Gary W CaldwellSummaryAffiliation: Johnson and Johnson Pharmaceutical Research and Development Country: USA Publications
| Collaborators |
Detail Information
Publications
Screening for reactive intermediates and toxicity assessment in drug discoveryGary W Caldwell
Johnson and Johnson Pharmaceutical Research and Development LLC, Drug Discovery, Spring House, PA 19477, USA
Curr Opin Drug Discov Devel 9:47-60. 2006..Current and future strategies for the proper sequencing of these assays in a drug discovery environment are also discussed...
The use of the suicide CYP450 inhibitor ABT for distinguishing absorption and metabolism processes in in-vivo pharmacokinetic screensGary W Caldwell
Johnson and Johnson Pharmaceutical Research and Development, L L C, Welsh and McKean Roads, P O Box 776, Spring House, PA 19477, USA
Eur J Drug Metab Pharmacokinet 30:75-83. 2005..Due to the ease of preparing and interpreting PK data from ABT-treated rats, is suggested that this assay could be used as an alternative to in vivo cannulation assays...
Unbiased high-throughput screening of reactive metabolites on the linear ion trap mass spectrometer using polarity switch and mass tag triggered data-dependent acquisitionZhengyin Yan
Division of Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, LLC, Spring House, Pennsylvania 19477, USA
Anal Chem 80:6410-22. 2008..Additionally, this methodology can potentially be applied to triple quadrupole or hybrid triple quadrupole mass spectrometers...
Isobaric metabolite interferences and the requirement for close examination of raw data in addition to stringent chromatographic separations in liquid chromatography/tandem mass spectrometric analysis of drugs in biological matrixZhengyin Yan
Division of Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, LLC, Spring House, PA 19477, USA
Rapid Commun Mass Spectrom 22:2021-8. 2008..Two examples described in this article remind us that quality data require both adequate chromatographic separations and close examination of raw data in LC/MS/MS analyses of drugs in biological matrix...
Use of stable isotope labeled probes to facilitate liquid chromatography/mass spectrometry based high-throughput screening of time-dependent CYP inhibitorsMalini Dasgupta
Division of Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, Spring House, PA 19477, USA
Rapid Commun Mass Spectrom 24:2177-85. 2010....
Biotransformation of geldanamycin and 17-allylamino-17-demethoxygeldanamycin by human liver microsomes: reductive versus oxidative metabolism and implicationsWensheng Lang
Johnson and Johnson Pharmaceutical Research and Development, LLC, P O Box 776, Welsh and McKean Roads, Spring House, PA 19477, USA
Drug Metab Dispos 35:21-9. 2007..The results provide direct evidence for understanding the 17-substituent effects of these benzoquinone ansamycins on their phase I metabolism, reactivity with glutathione, and acute hepatotoxicity...
Rapid detection and characterization of minor reactive metabolites using stable-isotope trapping in combination with tandem mass spectrometryZhengyin Yan
Division of Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, LLC, Spring House, PA 19477, USA
Rapid Commun Mass Spectrom 19:3322-30. 2005..In comparison with existing methods, this method is sensitive, efficient, and suitable for rapid screening and more complete profiling of reactive metabolites...
Liquid chromatographic and tandem mass spectrometric assay for evaluation of in vivo inhibition of rat brain monoamine oxidases (MAO) A and B following a single dose of MAO inhibitors: application of biomarkers in drug discoveryWensheng Lang
Johnson and Johnson Pharmaceutical Research and Development, Drug Discovery, Welsh and McKean Roads, Spring House, PA 19477, USA
Anal Biochem 333:79-87. 2004..The LC/MS/MS method is useful not only for the determination of inhibitory potency but also for the differentiation of the selectivity of a MAO inhibitor against rat brain MAO A and B in vivo...
Bioactivation of 4-methylphenol (p-cresol) via cytochrome P450-mediated aromatic oxidation in human liver microsomesZhengyin Yan
Division of Drug Discovery, R2013, Johnson and Johnson Pharmaceutical Research and Development, LLC, Welsh and McKean Roads, Spring House, Pennsylvania 19477 0779, USA
Drug Metab Dispos 33:1867-76. 2005..Implications of the newly identified reactive metabolite in p-cresol-induced toxicity remain to be investigated in the future...
Distribution and metabolism of the antipsychotic agent mazapertine succinate in ratsGary W Caldwell
Johnson and Johnson Pharmaceutical Research and Development, L L C, Spring House, PA 19477, USA
J Pharm Biomed Anal 41:500-9. 2006..Metabolites were formed by phenyl hydroxylation, piperidyl oxidation, O-dealkylation, N-dephenylation, oxidative N-debenzylation and glucuronide conjugation...
Allometric scaling of pharmacokinetic parameters in drug discovery: can human CL, Vss and t1/2 be predicted from in-vivo rat data?Gary W Caldwell
Johnson and Johnson Pharmaceutical Research and Development, L.L.C. Drug Discovery, Spring House, PA 19477, USA
Eur J Drug Metab Pharmacokinet 29:133-43. 2004....
Evaluation of the effect of oxygen exposure on human liver microsomal metabolism of mitomycin C in the presence of glutathione using liquid chromatography-quadrupole time of flight mass spectrometryWensheng Lang
Johnson and Johnson Pharmaceutical Research and Development, Welsh and McKean Roads, Spring House, PA 19477, USA
Anal Biochem 343:268-76. 2005..These findings provide direct evidence for understanding the fate of oxygen-sensitive metabolic deactivation of MC by GSH...
ADME optimization and toxicity assessment in early- and late-phase drug discoveryGary W Caldwell
Johnson and Johnson Pharmaceutical Research and Development, L L C Drug Discovery Department Welsh and McKean Roads, P O Box 776, Spring House, PA 19477, USA
Curr Top Med Chem 9:965-80. 2009..Understanding the false positive rates of these drug discovery preclinical assays is a must in reducing attrition rates in development...
Application of flow NMR to an open-access pharmaceutical environmentGregory C Leo
Johnson and Johnson Pharmaceutical Research and Development, LLC, Welsh and McKean Roads, P O Box 776, Spring House, Pennsylvania 19477 0776, USA
Anal Chem 75:1954-7. 2003..The protocol we present, using a single push solvent, contributes to the application of flow NMR in hands-on medicinal chemistry environments...
The application of nuclear magnetic resonance-based metabonomics to the dominant-submissive rat behavioral modelGregory C Leo
Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, Spring House, PA 19477 0776, USA
Anal Biochem 339:174-8. 2005..Measurements of galactose showed that the amount present in the urine correlated with the time spent in the feeder zone, thereby supporting the time criterion established for the DSR model...
Detection of a novel reactive metabolite of diclofenac: evidence for CYP2C9-mediated bioactivation via arene oxidesZhengyin Yan
Division of Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, LLC, Spring House, PA 19477 0779, USA
Drug Metab Dispos 33:706-13. 2005..This mechanism is consistent with the structural modeling of the CYP2C9-diclofenac complex, which reveals that both the C-3' and C-4' of the dichlorophenyl ring are proximate to the heme group...
An unusual intramolecular transfer of the fluorobenzyl cation between two remote amidic nitrogen atoms induced by collision in the gas phaseZhengyin Yan
Division of Drug Discovery, Johnson and Johnson Pharmaceutical R and D, LLC, Spring House, PA 19477, USA
Rapid Commun Mass Spectrom 26:49-60. 2012....
Stable-isotope trapping and high-throughput screenings of reactive metabolites using the isotope MS signatureZhengyin Yan
Division of Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, LLC, Spring House, Pennsylvania 19477, USA
Anal Chem 76:6835-47. 2004..More importantly, this study has demonstrated the feasibility of the current method for completely automated detection of reactive metabolites via computer-assisted pattern recognition...
Cone voltage induced in-source dissociation of glucuronides in electrospray and implications in biological analysesZhengyin Yan
Division of Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, LLC, Spring House, PA 19477, USA
Rapid Commun Mass Spectrom 17:1433-42. 2003..This approach has been proven to be effective in the analysis of more than 100 glucuronides generated from in vitro microsomal incubations...
A high-throughput monoamine oxidase inhibition assay using liquid chromatography with tandem mass spectrometryZhengyin Yan
Division of Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, LLC, Spring House, PA 19477 0779, USA
Rapid Commun Mass Spectrom 18:834-40. 2004..The results suggest that this method is very robust and can be used as a generic approach to screen for MAO inhibitors in drug discovery...
High-content assays for evaluating cellular and hepatic diacylglycerol acyltransferase activityJenson Qi
Johnson and Johnson Pharmaceutical Research and Development, LLC, Spring House, PA, USA
J Lipid Res 51:3559-67. 2010..This DGAT1-selective assay will enable researchers to discern differences between the roles of DGAT1 and DGAT2 in TG synthesis in vitro and in vivo...
