Pharmacology and Metabolomics Core

Pharmacology and Metabolomics Core

Mission of the Core

To provide state-of-the-art bioanalytic technology and a broad range of pharmacology expertise to enable evaluation of critical pharmacological endpoints in clinical trials and preclinical studies.

The Pharmacology and Metabolomics Core is supported, in part, by NIH Center grant P30 CA022453 to the Karmanos Cancer Institute at Wayne State University.

Core Services Available

The Pharmacology Core offers the following services based on fee-for-service:

  • Biospecimen Processing Service: Provides a centralized resource for the acquisition, processing, and shipment of patient specimens (including blood and bone marrow samples) that are required for evaluation of pharmacokinetics or pharmacodynamics according to clinical protocol specifications. All specimens are collected from patients who provided informed consent following an Institutional Review Board approved protocol. Specimen handling, processing, and shipment are in compliance with good laboratory practice procedures, approved standard operating procedures, and regulatory requirements to ensure sample integrity and quality. A secure database that includes detailed information on the acquisition, processing, distribution of samples, along with related clinical data, is maintained.

  • Bioanalysis Service: provides development, validation, and implementation of liquid chromatography coupled with tandem mass spectrometer (LC-MS/MS) based analytical methods for quantitative determination of drugs and their metabolites as well as and endogenous chemicals (metabolites) in biological samples (including biofluid, tissue, cell culture samples). Method validation is provided based on the United States Food and Drug Administration Guidance for Bioanalytical Method Validation to ensure that a particular method is specific, sensitive, reliable, reproducible, and suitable for the intended analytical use. Rigorous quality assurance and quality control are provided for the analyses of clinical and preclinical samples.

  • LC-MS/MS Based Targeted Metabolomics: Aims to measure predefined groups of metabolites that are involved in central metabolic pathways including carbohydrate, protein, and lipid metabolism. We strive to provide GLP-quality analytical service at competitive prices, and regularly customize assays to meet investigators’ needs. Our services spans from initial consultation for study design and sample collection, to sample preparation and instrumental analysis, and to assistance with data analysis

In addition, the Core provides a broad range of pharmacological support including:

  • Pharmacokinetic study design to assist study design for pharmacokinetic evaluation in clinical and preclinical studies

  • Pharmacokinetic data analysis and modeling to characterize drug pharmacokinetics using traditional compartmental or non-compartmental analysis, nonlinear mixed-effect (population) pharmacokinetic modeling, or physiologically based pharmacokinetic modeling approaches

  • In vitro drug metabolism studies to determine metabolic pathways and potential drug-drug

Pricing

For pricing see the Pharmacology Core iLabs website here.

Pharmacology Core Instrumentation

Major analytical instrumentation includes:

  • B SCIEX QTRAP 6500 LC-MS/MS system: Consisting of an enhanced high performance hybrid triple quadrupole/linear ion trap mass spectrometer, interfaced with a SHIMADZU Nexera UPLC system, and associated software for operation and data analysis (AnalystTM for system control and data acquisition/processing; LightSightTM for metabolite identification).
  • Waters Xevo TQ-XS LC-MS/MS system: Consisting of a Waters AQUITY UPLC system coupled with a Waters Xevo TQ-XS triple quadrupole mass spectrometer, and associated software for operation and data analysis (MassLynxTM for system control and data acquisition and processing).

Major instrumentation for sample processing and storage includes:

  • Revco -300C and -800C freezers with liquid nitrogen have alarms and temperature chart recorders for the proper documentation of storage conditions
  • SpeedVac vacuum concentrator (Thermo Fisher Scientific)
  • Centrifuges include 1 Beckman Coulter GS-15R, 1 Beckman Allegra 21, and 2 Beckman Allegra X-22R
  • Other instrumentation includes homogenizers, sonicators, incubators, shakers, water bath

Software for pharmacokinetic data analysis and metabolomics data analysis:

  • WinNonlin (Pharsight Corp., Mountain View, CA)
  • NONMEM (ICON Development Solutions, Ellicott City, MD)
  • Simcyp® Physiologically based pharmacokinetic modeling software (Simcyp Limited, United Kingdom)
  • Online free software for metabolomics data analysis: MetaboAnalyst

Contact

Jing Li, Ph.D.
Director, Pharmacology and Metabolomics Core
313-576-8258
lijin@karmanos.org

Richard Wiegand, MS, Che
Manager, Pharmacology and Metabolomics Core
313-576-8244
wiegandr@karmanos.org

Pharmacology Core Selected Publications

Quantitative analysis of intracellular nucleoside triphosphates and other polar metabolites using ion pair reversed-phase liquid chromatography coupled with tandem mass spectrometry. J Chromatogr B 2015 (in press)
Authors: Wu J, Zhang Y, Wiegand R, Wang J, Bepler G, and Li J.

Complex disease-, gene-, and drug-drug interactions: impact of renal function, CYP2D6 status, and OCT2 activity on the pharmacokinetics of veliparib.  Clin Cancer Res 2014 Jun 19. [Epub ahead of print] (PMID: 24947923)
Authors: Li J, Kim S, Sha X, Wiegand R, Wu J, and LoRusso P.

In vitro metabolism and drug-drug interaction potential of UTL-5g, a novel chemo- and radio-protective agent.  Drug Metab Dispos 2014; 42(12): 2058-2067 (PMID: 25249693)
Authors: Wu J, Shaw J, Dubaisi S, Valeriote F, and Li J.

A stable isotope-labeled internal standard is essential for correcting for the interindividual variability in the recovery of lapatinib from cancer patient plasma in quantitative LC-MS/MS analysis.  J Chromatogr B 2013; 941: 100-108 (PMID: 24189203)
Authors: Wu J, Wiegand R, LoRusso P, Li J.

A phase 1 study of folate conjugate EC145 (vintafolide) in patients with refractory solid tumors.  J Clin Oncol 2012; 30: 4011-4016 (PMID: 23032618)
Authors: LoRusso P, Edelman M, Bever S, Forman K, Pilat M, Quinn M, Li J, Heath E, Malburg L, Klein P, Leamon C, Messmann R, and Sausville E.

Implications of plasma protein binding for pharmacokinetics and pharmacodynamics of the γ-secretase inhibitor RO4929097.  Clin Cancer Res. 2012; 18: 2066-2079 (PMID: 22351688)
Authors: Wu J, LoRusso P, Matherly L, Li J.

Simultaneous determination of FAU [1-(2’-deoxy-2’-fluoro-β-D-arabinofuranosyl) uracil] and FMAU [1-(2’-deoxy-2’-fluoro- β-D-arabinofuranosyl 5-methyluracil] in human plasma by liquid chromatography/tandem mass spectrometry. J Chromatogr B 2012; 891-892: 64-70 (PMID: 22410089)
Authors: Wiegand R, Wu J, Shields AF, LoRusso P, Li J.

Validation and implementation of a liquid chromatography/tandem mass spectrometry assay for quantitation of the total and unbound RO4929097, a γ-secretase inhibitor targeting Notch signaling, in human plasma.  J Chromatogr B 2011; 879: 1537-1543 (PMID: 21497565)
Authors: Wu J, Wiegand R, LoRusso P, Li J.

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