Mingshe Zhu

Summary

Affiliation: Bristol-Myers Squibb
Country: USA

Publications

  1. ncbi request reprint Protein covalent binding of maxipost through a cytochrome P450-mediated ortho-quinone methide intermediate in rats
    Donglu Zhang
    Department of Preclinical Candidate Optimization, P O Box 4000, Bristol Myers Squibb, Princeton, NJ 08543, USA
    Drug Metab Dispos 31:837-45. 2003
  2. ncbi request reprint Cytochrome P450 3A-mediated metabolism of buspirone in human liver microsomes
    Mingshe Zhu
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    Drug Metab Dispos 33:500-7. 2005
  3. ncbi request reprint Screening and identification of GSH-trapped reactive metabolites using hybrid triple quadruple linear ion trap mass spectrometry
    Joanna Zheng
    Department of Bioanalytical Research, Bristol Myers Squibb, Princeton, New Jersey 08543, USA
    Chem Res Toxicol 20:757-66. 2007
  4. ncbi request reprint Analysis of low level radioactive metabolites in biological fluids using high-performance liquid chromatography with microplate scintillation counting: method validation and application
    Mingshe Zhu
    Biotransformation Department, Pharmaceutical Candidate Opertimization, Bristol Myers Squibb, Princeton, NJ 08540 4000, USA
    J Pharm Biomed Anal 39:233-45. 2005
  5. ncbi request reprint Involvement of multiple cytochrome P450 and UDP-glucuronosyltransferase enzymes in the in vitro metabolism of muraglitazar
    Donglu Zhang
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb, P O Box 4000, Princeton, NJ 08543, USA
    Drug Metab Dispos 35:139-49. 2007
  6. ncbi request reprint Comparative metabolism of radiolabeled muraglitazar in animals and humans by quantitative and qualitative metabolite profiling
    Donglu Zhang
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb, P O Box 4000, Princeton, NJ 08543, USA
    Drug Metab Dispos 35:150-67. 2007
  7. ncbi request reprint Detection and structural characterization of glutathione-trapped reactive metabolites using liquid chromatography-high-resolution mass spectrometry and mass defect filtering
    Mingshe Zhu
    Department of Biotransformation, Pharmaceutical Candidate Optimization, Bristol Myers Squibb Research and Development, Princeton, New Jersey 08543, USA
    Anal Chem 79:8333-41. 2007
  8. ncbi request reprint Development and full validation of six inhibition assays for five major cytochrome P450 enzymes in human liver microsomes using an automated 96-well microplate incubation format and LC-MS/MS analysis
    Ming Yao
    Department of Biotransformation, Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 4000, Princeton, NJ 08543, USA
    J Pharm Biomed Anal 44:211-23. 2007
  9. doi request reprint Rapid screening of glutathione-trapped reactive metabolites by linear ion trap mass spectrometry with isotope pattern-dependent scanning and postacquisition data mining
    Li Ma
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb Research and Development, Princeton, New Jersey 08543, USA
    Chem Res Toxicol 21:1477-83. 2008
  10. ncbi request reprint Rapid and sensitive characterization of the metabolite formation enzyme kinetics of radiolabeled drugs using stop-flow liquid radiochromatography
    Weiping Zhao
    Bristol Myers Squibb, Biotransformation, PCO, Princeton, NJ 08540 4000, USA
    Drug Metab Lett 2:41-6. 2008

Detail Information

Publications36

  1. ncbi request reprint Protein covalent binding of maxipost through a cytochrome P450-mediated ortho-quinone methide intermediate in rats
    Donglu Zhang
    Department of Preclinical Candidate Optimization, P O Box 4000, Bristol Myers Squibb, Princeton, NJ 08543, USA
    Drug Metab Dispos 31:837-45. 2003
    ....
  2. ncbi request reprint Cytochrome P450 3A-mediated metabolism of buspirone in human liver microsomes
    Mingshe Zhu
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    Drug Metab Dispos 33:500-7. 2005
    ..Taken together, these data suggest that CYP3A, mostly likely CYP3A4, is primarily responsible for the metabolism of buspirone in HLMs...
  3. ncbi request reprint Screening and identification of GSH-trapped reactive metabolites using hybrid triple quadruple linear ion trap mass spectrometry
    Joanna Zheng
    Department of Bioanalytical Research, Bristol Myers Squibb, Princeton, New Jersey 08543, USA
    Chem Res Toxicol 20:757-66. 2007
    ..Also, it can be applied in conjunction with the PI or NL scan as a comprehensive method for the analysis of reactive metabolites in a drug discovery setting...
  4. ncbi request reprint Analysis of low level radioactive metabolites in biological fluids using high-performance liquid chromatography with microplate scintillation counting: method validation and application
    Mingshe Zhu
    Biotransformation Department, Pharmaceutical Candidate Opertimization, Bristol Myers Squibb, Princeton, NJ 08540 4000, USA
    J Pharm Biomed Anal 39:233-45. 2005
    ..The data from this study strongly suggest that HPLC in combination with TopCount is a viable alternative analytical tool for detection and quantification of low levels of radioactive metabolites in biological fluids...
  5. ncbi request reprint Involvement of multiple cytochrome P450 and UDP-glucuronosyltransferase enzymes in the in vitro metabolism of muraglitazar
    Donglu Zhang
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb, P O Box 4000, Princeton, NJ 08543, USA
    Drug Metab Dispos 35:139-49. 2007
    ....
  6. ncbi request reprint Comparative metabolism of radiolabeled muraglitazar in animals and humans by quantitative and qualitative metabolite profiling
    Donglu Zhang
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb, P O Box 4000, Princeton, NJ 08543, USA
    Drug Metab Dispos 35:150-67. 2007
    ..Disposition and metabolic pathways were qualitatively similar in rats, dogs, monkeys, and humans...
  7. ncbi request reprint Detection and structural characterization of glutathione-trapped reactive metabolites using liquid chromatography-high-resolution mass spectrometry and mass defect filtering
    Mingshe Zhu
    Department of Biotransformation, Pharmaceutical Candidate Optimization, Bristol Myers Squibb Research and Development, Princeton, New Jersey 08543, USA
    Anal Chem 79:8333-41. 2007
    ..The GSH adduct screening capability of the MDF approach, together with the utility of accurate mass MS/MS information in structural elucidation, makes high-resolution LC-MS a useful tool for analyzing reactive metabolites...
  8. ncbi request reprint Development and full validation of six inhibition assays for five major cytochrome P450 enzymes in human liver microsomes using an automated 96-well microplate incubation format and LC-MS/MS analysis
    Ming Yao
    Department of Biotransformation, Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 4000, Princeton, NJ 08543, USA
    J Pharm Biomed Anal 44:211-23. 2007
    ..The high quality and throughput of these assays make them ideally suited for providing information for decision making in late drug discovery and early development and for providing labeling input for new drug registrations...
  9. doi request reprint Rapid screening of glutathione-trapped reactive metabolites by linear ion trap mass spectrometry with isotope pattern-dependent scanning and postacquisition data mining
    Li Ma
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb Research and Development, Princeton, New Jersey 08543, USA
    Chem Res Toxicol 21:1477-83. 2008
    ..Overall, this analytical approach provides a simple and efficient means for screening for reactive metabolites using a linear ion trap LC/MS platform...
  10. ncbi request reprint Rapid and sensitive characterization of the metabolite formation enzyme kinetics of radiolabeled drugs using stop-flow liquid radiochromatography
    Weiping Zhao
    Bristol Myers Squibb, Biotransformation, PCO, Princeton, NJ 08540 4000, USA
    Drug Metab Lett 2:41-6. 2008
    ..The enzyme kinetic parameters of muraglitazar glucuronidation determined by stop-flow RFD were comparable with those determined by microplate scintillation counting (MSC)...
  11. ncbi request reprint Integrated strategies for assessment of metabolite exposure in humans during drug development: analytical challenges and clinical development considerations
    Mingshe Zhu
    Biotransformation, Department of Pharmaceutical Candidate Optimization, Bristol Myers Squibb Co, Princeton, NJ 08543, USA
    Biopharm Drug Dispos 30:163-84. 2009
    ..A one-size-fits-all approach is rarely the best use of resources...
  12. doi request reprint Detection of novel reactive metabolites of trazodone: evidence for CYP2D6-mediated bioactivation of m-chlorophenylpiperazine
    Bo Wen
    Department of Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Princeton, New Jersey, USA
    Drug Metab Dispos 36:841-50. 2008
    ....
  13. doi request reprint Investigation of bioactivation of ticlopidine using linear ion trap/orbitrap mass spectrometry and an improved mass defect filtering technique
    Qian Ruan
    Department of Biotransformation, Pharmaceutical Candidate Optimization, Bristol Myers Squibb, New Jersey 08543, USA
    Chem Res Toxicol 23:909-17. 2010
    ..Finally, a quick check of isotopic doublets and full examination of isotope fingerprints in the accurate mass were introduced to screen out false positives and enhance the identification of low abundant GSH adducts...
  14. doi request reprint Rapid screening and characterization of drug metabolites using multiple ion monitoring dependent product ion scan and postacquisition data mining on a hybrid triple quadrupole-linear ion trap mass spectrometer
    Ming Yao
    Department of Biotransformation, Bristol Myers Squibb Pharmaceutical Research and Development, PO Box 4000, Princeton, NJ 08543, USA
    Rapid Commun Mass Spectrom 23:1683-93. 2009
    ..Additionally, it enabled metabolite detection and MS/MS acquisition in a single injection. This approach is potentially useful in high-throughout screening of metabolic soft spots and reactive metabolites at the drug discovery stage...
  15. doi request reprint Rapid detection and characterization of in vitro and urinary N-acetyl-L-cysteine conjugates using quadrupole-linear ion trap mass spectrometry and polarity switching
    Wenying Jian
    Bioanalysis and Discovery Analytical Research and Biotransforamtion, Pharmaceutical Research and Development, Bristol Myers Squibb, Princeton, New Jersey 08543, USA
    Chem Res Toxicol 22:1246-55. 2009
    ....
  16. doi request reprint Rapid screening and characterization of drug metabolites using a multiple ion monitoring-dependent MS/MS acquisition method on a hybrid triple quadrupole-linear ion trap mass spectrometer
    Ming Yao
    Department of Biotransformation, Bristol Myers Squibb Pharmaceutical Research and Development, PO Box 4000, Princeton, NJ 08543, USA
    J Mass Spectrom 43:1364-75. 2008
    ..Overall, MIM-EPI significantly enhanced the metabolite identification capability of the hybrid triple quadrupole-linear ion trap LC/MS...
  17. ncbi request reprint An integrated method for metabolite detection and identification using a linear ion trap/Orbitrap mass spectrometer and multiple data processing techniques: application to indinavir metabolite detection
    Qian Ruan
    Department of Biotransformation, Bristol Myers Squibb Company, Princeton, NJ, USA
    J Mass Spectrom 43:251-61. 2008
    ....
  18. ncbi request reprint Detection and characterization of metabolites in biological matrices using mass defect filtering of liquid chromatography/high resolution mass spectrometry data
    Mingshe Zhu
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, USA
    Drug Metab Dispos 34:1722-33. 2006
    ....
  19. ncbi request reprint Mass defect profiles of biological matrices and the general applicability of mass defect filtering for metabolite detection
    Haiying Zhang
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb Research and Development, Princeton, NJ 08543, USA
    Rapid Commun Mass Spectrom 22:2082-8. 2008
    ..In addition, the mass defect profiles of the biological matrices allow for prediction of the effectiveness of MDF for certain applications, and for designing specific MDF windows for selective detection of drug metabolites...
  20. doi request reprint An algorithm for thorough background subtraction from high-resolution LC/MS data: application to the detection of troglitazone metabolites in rat plasma, bile, and urine
    Haiying Zhang
    Biotransformation, Bristol Myers Squibb Research and Development, Princeton, NJ 08543, USA
    J Mass Spectrom 43:1191-200. 2008
    ....
  21. doi request reprint Mass defect filter technique and its applications to drug metabolite identification by high-resolution mass spectrometry
    Haiying Zhang
    Department of Biotransformation, Bristol Myers Squibb Research and Development, Princeton, NJ 08543, USA
    J Mass Spectrom 44:999-1016. 2009
    ..Advantages, limitations, and future applications are also discussed on MDF and its combinations with other data mining techniques for the detection and identification of drug metabolites...
  22. ncbi request reprint Disposition and metabolism of [14C]brasofensine in rats, monkeys, and humans
    Mingshe Zhu
    Department of Pharmaceutical Candidate Optimization, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, USA
    Drug Metab Dispos 36:24-35. 2008
    ..These primary metabolites and glucuronides of demethyl brasofensine (M1 and M2) were major circulating metabolites in humans and were also observed in rat and monkey plasma...
  23. doi request reprint High-throughput screening and characterization of reactive metabolites using polarity switching of hybrid triple quadrupole linear ion trap mass spectrometry
    Bo Wen
    Department of Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Princeton, New Jersey 08543, USA
    Anal Chem 80:1788-99. 2008
    ..More importantly, the PI-EPI approach is suitable for high-throughput screening of reactive metabolites in the drug discovery process...
  24. ncbi request reprint Amide N-glucuronidation of MaxiPost catalyzed by UDP-glucuronosyltransferase 2B7 in humans
    Donglu Zhang
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb Research Institute, Route 206 and Province Line Road, Princeton, NJ 08543, USA
    Drug Metab Dispos 32:545-51. 2004
    ..This N-glucuronide represents a fully characterized amide N-glucuronide, and glucuronidation at the nitrogen represents a newly identified conjugation reaction for UGT2B7...
  25. ncbi request reprint Discovering drugs through biological transformation: role of pharmacologically active metabolites in drug discovery
    Aberra Fura
    Bristol Myers Squibb, Pharmaceutical Research Institute, P O Box 5400, Princeton, New Jersey 08534, USA
    J Med Chem 47:4339-51. 2004
  26. doi request reprint In vitro screening of 50 highly prescribed drugs for thiol adduct formation--comparison of potential for drug-induced toxicity and extent of adduct formation
    Jinping Gan
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb Research and Development, Princeton, New Jersey 08543, USA
    Chem Res Toxicol 22:690-8. 2009
    ....
  27. ncbi request reprint Cyp2D6 catalyzes 5-hydroxylation of 1-(2-pyrimidinyl)-piperazine, an active metabolite of several psychoactive drugs, in human liver microsomes
    Nirmala Raghavan
    Pharmaceutical Candidate Optimization, P O Box 4000, Bristol Myers Squibb, Princeton, NJ 08543, USA
    Drug Metab Dispos 33:203-8. 2005
    ..Collectively, these results indicate that polymorphic CYP2D6 is responsible for the conversion of 1-PP to HO-1-PP...
  28. doi request reprint Bioactivation of coumarin in rat olfactory mucosal microsomes: Detection of protein covalent binding and identification of reactive intermediates through analysis of glutathione adducts
    Xiaoliang Zhuo
    Department of Biotransformation, Bristol Myers Squibb Company, Wallingford, CT 06492, USA
    Chem Biol Interact 181:227-35. 2009
    ..Our findings provide direct evidence for the formation of multiple coumarin reactive intermediates in rat OM, leading to protein covalent binding and GSH conjugation...
  29. ncbi request reprint A novel high-throughput automated chip-based nanoelectrospray tandem mass spectrometric method for PAMPA sample analysis
    Praveen V Balimane
    Bristol Myers Squibb, Princeton, NJ 08543, USA
    J Pharm Biomed Anal 39:8-16. 2005
    ..Thus, it has been demonstrated that nanoelectrospray analysis provides a highly efficient and accurate analytical methodology to analyze PAMPA samples generated in early drug discovery...
  30. pmc Drug metabolite profiling and identification by high-resolution mass spectrometry
    Mingshe Zhu
    Bristol Myers Squibb Pharmaceutical Company, Princeton, New Jersey 08543, USA
    J Biol Chem 286:25419-25. 2011
    ..Also, application of HR-MS-based strategies to key metabolite identification activities and future developments in the field are discussed...
  31. ncbi request reprint A strategy for metabolite identification using triple-quadrupole mass spectrometry with enhanced resolution and accurate mass capability
    Mohammed Jemal
    Bioanalytical Sciences, Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 191, New Brunswick, NJ 08903 0191, USA
    Rapid Commun Mass Spectrom 17:2732-40. 2003
    ....
  32. doi request reprint Strategy and its implications of protein bioanalysis utilizing high-resolution mass spectrometric detection of intact protein
    Qian Ruan
    Biotransformation, Bristol Myers Squibb Comapny, Route 206 and Province Line Road, Princeton, New Jersey 08543, USA
    Anal Chem 83:8937-44. 2011
    ..The current instrumentation limitations and potential advantages of this approach for the bioanalysis of large proteins are discussed...
  33. ncbi request reprint Structural elucidation of human oxidative metabolites of muraglitazar: use of microbial bioreactors in the biosynthesis of metabolite standards
    Donglu Zhang
    Pharmaceutical Candidate Optimization, Pharmaceutical Research Institute, Bristol Myers Squibb, P O Box 4000, Princeton, NJ 08543, USA
    Drug Metab Dispos 34:267-80. 2006
    ..This study demonstrated the utility of microbial bioreactors for the identification of metabolites...
  34. doi request reprint Reflecting on a decade of metabolite screening and monitoring
    Anne Francoise Aubry
    Analytical and Bioanalytical Development, Bristol Myers Squibb, Princeton, NJ 08540, USA
    Bioanalysis 6:651-64. 2014
    ..Case studies illustrate how decisions are made, how different scientific situations influence the assay choice, and what criteria may be set to continue or discontinue metabolite monitoring in later drug development. ..
  35. ncbi request reprint A rapid and sensitive LC/MS/MS assay for quantitative determination of digoxin in rat plasma
    Ming Yao
    Department of Metabolism and Pharmacokinetics, Bristol Myers Squibb Pharmaceutical Research Institute, F13 07, PO Box 4000, Princeton, NJ 08543, USA
    J Pharm Biomed Anal 32:1189-97. 2003
    ..7+/-3.9 and 105.9+/-2.3%, respectively. The present method was successfully applied to characterization of pharmacokinetic profiles of digoxin in rats after oral administration...
  36. doi request reprint Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s
    Bo Wen
    Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, CA 94304, United States
    Chem Biol Interact 173:59-67. 2008
    ..It is proposed that the arene oxide intermediate(s) may represent a rate-limiting step in the initiation of amitriptyline and nortriptyline-mediated hepatotoxicity...