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In Vivo MetID (Metabolite Profiling and Identification)

MetID studies in plasma, urine, feces, bile, tissues of animal and plasma, excreta of human reveal distribution information of drugs and their metabolites, which is used to evaluate the metabolites in circulation as well as their metabolic clearance pathways. Adequate knowledge of metabolic fate of a compound is critical in support of discovery and safety studies.

  • Overview

  • Assays

  • Case Study

  • Regulatory Guidance

  • Experience

  • Instruments and Software

  • FAQs

  • Related Resources

  • Related Services

Overview

The in vivo MetID platform at WuXi AppTec DMPK offers three types of metabolic studies for different experimental purposes: circulation and excreta metabolism study in animals, and clinical metabolism study. In addition, the established in vivo MetID platform has performed metabolite profiling and identification of lead compounds and drug candidates with a variety of structures, including conventional small molecules, high-polar and non-polar small molecules, natural products, nucleotides, Proteolysis-Targeting Chimeras (PROTACs*), polysaccharides, peptides, ADCs, PDCs, oligonucleotides, etc. Sample matrices include whole blood, plasma, urine, feces, bile, tissues, etc.

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Case Study

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      Metabolite profiles in plasma, urine, and feces of human

      Figure1

      Result: Figure 1 are metabolite profiling and ID results of pooled human plasma, urine and feces using LC/HRMS. The results indicate that the parent drug is the major pharmacological component exposed, while multiple minor metabolites are present in plasma. Metabolite M3 and M4 (glucuronidation) and M7 (mono-oxygenation metabolite) are most likely the major metabolites in urine and feces, suggesting that the formation of M3/M4 and M7 may be major metabolic clearance pathways in human. Several minor metabolic pathways lead to minor metabolites in urine and feces. The parent drug is a major drug-related component in feces, which may be unabsorbed, excreted into bile and/or from hydrolysis of M3 and M4 and other glucuronides in feces. The parent drug is a minor drug-related component in urine, suggesting that direct excretion of the parent drug from kidney to urine is not a major clearance pathway.

Experience

  • 16+

    Years of experience

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  • 500+

    Submissions of IND applications

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  • 2000+

    Screening projects

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Instruments and Software

  • Instruments

  • Software

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      Thermo Orbitrap Eclipse™ Tribrid™

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      Thermo Orbitrap Exploris™ 480

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      Thermo Q-Exactive™ HF

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      Waters VION™ IMS QTof

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      Thermo Q-Exactive™ Plus

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      Thermo Q-Exactive™

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      Therno LTQ Orbitrap XL

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      Waters Xevo®G2 QTof

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      Solid scintillation counter: off-line detection of radioactivity

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      Liquid scintillation counter: total radioactivity detection

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      On-line detection of radioactivity

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      Thermo Scientific™ Compound Discoverer™

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      Thermo Scientific™ Mass Frontier™

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      Thermo Scientific™ Metworks™

    • Waters MetaboLynx.png

      Waters MetaboLynxTM

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      Mass Analytical Mass-MetaSite

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      Waters UNIFI®

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      Thermo Scientific™ Biopharma Finder™

FAQs

  • What is in vivo metabolite identification?

    Metabolite profiling and identification studies in plasma, urine, feces, bile, tissues of animal and plasma, excreta of human are conducted to reveal the distribution information of drugs and their metabolites, and to evaluate metabolites in the circulation and their metabolic clearance pathways.

  • What role does in vivo metabolite identification play in safety assessments?

    Metabolite detection and identification of a non-radiolabeled drug in animals and human are often conducted in late discovery and early clinical study, respectively. Profiling and identification of metabolites in plasma may provide the information on what metabolites are exposed to animals and human, what are their abundances relative to the parent drug and what are major metabolites in animal or human circulation. Comparison between the metabolite exposure in human and toxicological species can verify whether the safety of major metabolites in human is adequately evaluated in toxicological species. Profiling and identification of metabolites in urine, feces and/or bile may provide the information of metabolic clearance pathways in animals and human, which can be utilized to correlate in vitro and in vivo metabolism.

Related Resources

Reference

  1. 1.

    C. E. Hop, Z. Wang, Q. Chen, G. Kwei, Plasma-Pooling Methods to Increase Throughput for in vivo Pharmacokinetic Screening, J. Pharm. Sci., 87 (1998) 901-903.

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