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🧪 Drug Discovery/Biochemical Probes · Method

ADME/Drug Metabolism

Assess absorption, distribution, metabolism, excretion
🎯 Difficulty ★★★ Advanced Duration About 1–2 weeks 🎯 Use Evaluate metabolic stability and pharmacokinetics of drug candidates to predict druggability
📖 Principle
Use liver microsomes/hepatocytes or in vivo to model drug metabolism, quantify parent and metabolites over time by LC-MS
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📋 Workflow

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1

In vitro metabolism incubation

2–4 h
Incubate drug with liver microsomes/hepatocytes and cofactor (NADPH) at multiple time points
💡 Tip Include no-NADPH and no-protein controls
⚠️ Caution Optimize protein and substrate concentrations
🧪 Materials for this step (click to shop by spec/brand)
2

Quench and sample preparation

1 h
Quench with organic solvent to precipitate protein, centrifuge and collect supernatant
💡 Tip Include internal standard for precision
⚠️ Caution Handle on ice to prevent degradation
🧪 Materials for this step (click to shop by spec/brand)
3

LC-MS analysis

2–4 h
Use LC-MS to separate and quantify parent drug and metabolites
💡 Tip MRM mode improves sensitivity
⚠️ Caution Validate method for reliable quantification
🧪 Materials for this step (click to shop by spec/brand)
4

Data analysis and evaluation

2 h
Calculate metabolic half-life, clearance and intrinsic clearance to evaluate metabolic stability
💡 Tip Integrate with in vivo PK data
⚠️ Caution Assess cross-species predictability
🧪 Materials for this step (click to shop by spec/brand)

⚠️ 5 Common Beginner Mistakes

  • Wrong protein/cofactor bias metabolic rate
  • Insufficient time points hamper half-life
  • Matrix effect disturbs MS quantification
  • Missing metabolite standards limit profiling
  • In vitro-in vivo extrapolation is challenging

❓ FAQ

+Microsomes vs hepatocytes?
Microsomes enriched in phase I are fast; hepatocytes retain phase I/II and transporters for holistic view.
+Poor metabolic stability?
Optimize structure to block soft spots, reduce lipophilicity or prodrug strategies.
+What is clearance?
Volume of drug cleared per unit time, governing dosing frequency and steady-state exposure.

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Data authenticity: Product categories from JW Supply Chain standard taxonomy; method→step→product connected. Last updated: 2026-08-23 · v3.0