ADME / DMPK / PK-PD Research Platforms

MS-Centric ADME/DMPK Research — From Metabolic Stability to Pharmaco-Proteomics, One Platform Covers the Full Drug Metabolism Continuum.

Understanding how a drug candidate is absorbed, distributed, metabolized, and excreted — and how those processes translate into pharmacokinetic and pharmacodynamic outcomes — is the backbone of informed drug development. We built the MassTarget ADME/DMPK/PK-PD Research Platform to cover this continuum end-to-end, using mass spectrometry as the unifying analytical engine.

Key Advantages:

Full-spectrum coverage — 11 sub-services spanning absorption, distribution, metabolism, excretion, and systems-level pharmaco-omics.
MS-native methodology — LC-MS/MS, HRMS, and RapidFire MS platforms purpose-built for ADME applications.
Integrated interpretation — From raw LC-MS/MS data to PK parameters, metabolite identification, and biological context.

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ADME DMPK mass spectrometry research platform overview

Why MS-Centric Capabilities Workflow Comparison Sample Demo FAQ

Why an MS-Centric ADME Platform for Your Drug Development Pipeline

Every drug development program faces the same inflection point: a promising lead compound enters preclinical characterization, and suddenly the questions multiply. How stable is it in human liver microsomes? Does it cross intestinal epithelium? What metabolites form, and are any of them toxic? Where does it distribute, and how is it cleared?

Most teams answer these questions by piecing together assays from different CROs — a metabolic stability study here, a permeability assay there, a separate MetID project with yet another provider. Each handoff introduces variability in methods, data formats, and interpretation standards. And when the data comes back inconsistent, the question becomes: is it the compound, or is it the assay?

The MassTarget ADME/DMPK platform was built to eliminate that uncertainty. It is a single, MS-native analytical engine covering the full ADME continuum — from absorption and distribution to metabolism, excretion, and systems-level pharmaco-omics — all running on the same LC-MS/MS, HRMS, and RapidFire MS infrastructure, under the same QC framework, interpreted by the same scientific team.

What this means for your program:

No assay handoff gaps — Metabolic stability, permeability, protein binding, MetID, PK bioanalysis, and pharmaco-omics all share the same analytical platform. Data from one assay feeds directly into the next, with consistent methodology and traceable QC.
MS-native, not MS-as-add-on — Mass spectrometry is the analytical core of every assay, not a technique bolted onto a general bioanalytical lab. This means deeper expertise in method development for challenging compounds — covalent binders, reactive metabolites, natural products, and novel modalities.
Scalable by design — Start with a single metabolic stability screen in human liver microsomes. Expand to multi-species comparison, add MetID, then build a full ADME panel. Add pharmaco-metabolomics or pharmaco-proteomics at any stage. All within the same platform, with data that accumulates rather than fragments.
Regulatory-ready from day one — Methods are developed within the ICH M10 framework, so the data you generate at early discovery stages remains defensible when you move toward IND-enabling studies.

Platform Capabilities: MS-Centric ADME Services

Absorption: Permeability and Binding

Oral bioavailability depends on two key factors: how well a compound crosses the intestinal epithelium and how much remains free in circulation. We assess both using LC-MS/MS workflows developed and optimized for each compound.

Drug Permeability (Caco-2/PAMPA) MS — Our Caco-2 bidirectional transport assay measures apparent permeability (Papp) in both apical-to-basolateral and basolateral-to-apical directions, providing efflux ratio data to identify P-glycoprotein or BCRP substrate activity. For early-stage screening, we offer the parallel artificial membrane permeability assay (PAMPA) as a higher-throughput alternative. Both assays are analyzed by LC-MS/MS, eliminating the need for radiolabeled or fluorescent compounds.

Plasma Protein Binding MS — Using equilibrium dialysis, we determine the unbound fraction (fu) of your compound in plasma from multiple species (human, rat, mouse, dog, monkey). The free drug concentration is the pharmacologically relevant species, making this a critical input for PK/PD modeling.

Tissue Binding MS — For compounds with high tissue affinity or distribution concerns, we measure tissue binding using a modified equilibrium dialysis or ultrafiltration approach, providing tissue-to-plasma partition coefficients (Kp).

Distribution and Excretion

Understanding where a drug goes after systemic absorption — and how it is eliminated — is essential for predicting efficacy and toxicity. Our distribution assays include tissue binding measurements and LC-MS/MS-based quantitation of drug levels in target organs, complementing standard plasma PK with organ-level data.

For excretion profiling, our LC-MS/MS bioanalysis services support method development and validation per ICH M10 guidance, quantitation of parent compound and metabolites in plasma, serum, urine, bile, and tissue homogenates, and PK parameter calculation (Cmax, Tmax, AUC, t1/2, CL, Vd) using non-compartmental or compartmental analysis.

Metabolism: Stability and MetID

The liver is the primary site of drug metabolism, and our metabolism module covers the full cascade from early stability screening to detailed structural characterization.

Metabolic Stability (Microsomes/S9/Hepatocytes) — We incubate your compound with liver microsomes, S9 fractions, or primary hepatocytes (human and preclinical species) and monitor parent compound depletion over time by LC-MS/MS. The output includes in vitro half-life (t1/2), intrinsic clearance (CLint), and scaled in vivo clearance predictions.

Metabolic Soft-Spot Analysis — Using high-resolution mass spectrometry (HRMS) with data-dependent acquisition, we identify the exact sites on the molecule where metabolism occurs, guiding medicinal chemistry efforts to block metabolically vulnerable positions.

Metabolite Identification (MetID) — We use HRMS/MS with multiple acquisition strategies to identify and structurally characterize phase I and phase II metabolites, with confidence levels based on MS/MS fragmentation patterns and retention time behavior.

Toxic Metabolite Detection — We offer trapping experiments using glutathione (GSH), cyanide, and other nucleophilic trapping agents, analyzed by HRMS for the detection and characterization of reactive metabolite-trapping agent conjugates.

Drug–Protein Adduct MS — For compounds with structural alerts for bioactivation, we provide covalent protein binding assays with LC-MS/MS-based proteomics to identify modified proteins and residues.

Systems-Level Profiling

Beyond individual ADME assays, we offer global profiling approaches that capture the broader biological response to drug treatment.

Pharmaco-Metabolomics — Untargeted LC-MS-based metabolomics to map metabolite changes in biofluids or tissues following drug administration, revealing on-target pharmacodynamic effects, off-target metabolic perturbations, and potential biomarker candidates.

Pharmaco-Proteomics — Proteome-wide expression profiling using LC-MS/MS to identify proteins whose abundance changes in response to drug treatment, providing a systems-level view of drug action and toxicity mechanisms.

Compound Flexibility

Our platform handles challenging chemotypes that general CROs may decline: covalent binders, reactive metabolites, natural products, and novel modalities. We routinely combine platforms within a single project — for example, using RapidFire MS for initial stability screening and HRMS for detailed metabolite characterization of selected compounds.

Our ADME/DMPK Workflow

Every ADME study at Creative Proteomics follows a structured five-step workflow designed to ensure data quality, reproducibility, and regulatory readiness.

Project Consultation

We begin with a detailed discussion of your compound's properties, development stage, and specific ADME questions. Based on this, we recommend the optimal assay panel — from a single metabolic stability screen to a comprehensive ADME + pharmaco-omics package.

Method Development & Validation

For each study, we develop and optimize an LC-MS/MS method specific to your compound, including tuning MS parameters, optimizing chromatographic separation, and establishing calibration curves, LLOQ, and QC samples. For regulated studies, we perform full method validation per ICH M10 guidelines.

Sample Processing & Acquisition

Samples are processed using appropriate techniques (protein precipitation, liquid-liquid extraction, solid-phase extraction) and analyzed on our LC-MS/MS or HRMS platforms. Each analytical batch includes calibration standards, QC samples at multiple concentrations, and blank matrix controls.

Data Processing & QC

Raw data is processed using validated software for peak integration, calibration curve regression, and concentration calculation. QC acceptance criteria include: accuracy within ±15% (±20% at LLOQ), precision ≤15% CV, and at least 67% of QC samples meeting acceptance criteria.

Interpretation & Report Delivery

Results are compiled into a comprehensive report that includes: experimental methods, raw and processed data tables, QC summary, calculated parameters (t1/2, CLint, Papp, fu, PK parameters), and a scientific interpretation section that places the data in the context of your program's development stage.

ADME DMPK mass spectrometry workflow from consultation to data delivery

Technology Comparison: ADME Analysis Platforms

Dimension	LC-MS/MS (Triple Quad)	HRMS (Orbitrap / Q-TOF)	RapidFire MS	Traditional Biochemical Assays
Throughput	High (2–5 min/sample)	Moderate (10–20 min/sample)	Very high (10–15 sec/sample)	High (plate-based)
Sensitivity	Excellent (sub-ng/mL LLOQ)	Good (ng/mL range)	Good (comparable to LC-MS/MS)	Variable (assay-dependent)
Selectivity	High (MRM mode)	Very high (full MS + MS/MS)	High (MRM mode)	Low-moderate (cross-reactivity risk)
Metabolite Coverage	Targeted only	Comprehensive (untargeted)	Targeted only	Not applicable
Data Depth	Quantitative (concentration)	Quantitative + structural	Quantitative (fast)	Single readout (e.g., fluorescence)
Best For	Routine quantitation, PK bioanalysis	MetID, soft-spot, pharmaco-omics	High-throughput ADME screening	Early-stage, label-dependent assays

For routine metabolic stability and PK bioanalysis, LC-MS/MS (QQQ) provides the best balance of throughput and sensitivity. For metabolite identification, soft-spot analysis, and pharmaco-omics, HRMS is the platform of choice. RapidFire MS is ideal for high-throughput ADME screening campaigns where sample-to-result speed is the priority.

Sample Requirements for ADME Studies

Assay Type	Sample Required	Quantity / Volume	Test System	Key Parameters Reported
Metabolic Stability	Compound (powder or DMSO stock)	1–10 µM final; 50–100 µL per time point	Liver microsomes / S9 / hepatocytes (human + preclinical species)	t_1/2, CL_int, scaled CL_hep, % remaining
Drug Permeability (Caco-2)	Compound (DMSO stock)	10 µM; 200–500 µL per compartment	Caco-2 cell monolayer (21-day culture)	P_app A→B, P_app B→A, efflux ratio, recovery
Plasma Protein Binding	Compound + plasma	1–10 µM; 200 µL plasma per species	Equilibrium dialysis (4–6 hr, 37 °C)	f_u (unbound fraction), % bound
Metabolite Identification (MetID)	In vivo or in vitro incubation samples	>50 µL or >100 mg tissue	Microsomes/hepatocytes (in vitro) or plasma/urine/bile (in vivo)	Metabolite structures, relative abundance, metabolic pathways
LC-MS/MS Bioanalysis	Plasma, serum, or tissue homogenate	>50 µL per time point; full PK profile	Calibrated LC-MS/MS method	Concentration-time data, PK parameters (C_max, AUC, t_1/2, CL, V_d)

Note: Specific requirements depend on compound properties and assay design. Contact our scientists to confirm the optimal sample preparation and quantity for your specific study.

Deliverables

Metabolic Stability Studies:

In vitro half-life (t_1/2) and intrinsic clearance (CL_int) per species
Scaled in vivo clearance predictions (CL_hep)
Species comparison summary
LC-MS/MS chromatograms and calibration data

Permeability and Binding Studies:

Apparent permeability (P_app) in both directions
Efflux ratio and transport mechanism assessment
Unbound fraction (f_u) in plasma and tissue
Recovery and membrane integrity data

Metabolite Identification Studies:

Full metabolite profile with extracted ion chromatograms
MS/MS fragmentation spectra for each metabolite
Proposed metabolite structures with confidence assignment
Metabolic pathway schematic
Comparison across species (if applicable)

PK Bioanalysis:

Validated LC-MS/MS method summary
Concentration-time data for each individual animal
PK parameters (non-compartmental or compartmental)
QC summary with accuracy and precision data

Pharmaco-Omics Studies:

Differential expression/abundance lists with statistical analysis
Pathway enrichment and network analysis
Raw data files for independent re-analysis

Why Choose MassTarget for ADME/DMPK Research?

Dimension	MassTarget ADME/DMPK Platform	Typical ADME CRO	Key Difference
Technology Core	MS-native platform — LC-MS/MS, HRMS, and RapidFire MS purpose-integrated for ADME	General CRO with LC-MS/MS as one of many techniques	Deeper MS expertise, better method optimization for challenging compounds
Service Breadth	11 sub-services from metabolic stability to pharmaco-proteomics	Standardized ADME package (stability, permeability, binding, MetID)	Single-provider coverage eliminates handoff between CROs
Data Interpretation	Integrated scientific interpretation connecting ADME data to PK/PD outcomes	Raw data or standard report format	Actionable insights, not just numbers
QC Transparency	Full QC data: calibration curves, accuracy/precision, matrix effects, recovery	Standard QC (may not share raw QC data)	Verifiable data quality for regulatory confidence
Compound Flexibility	Handles challenging chemotypes: covalent binders, reactive metabolites, natural products, novel modalities	May decline or struggle with non-standard compounds	Broader compound scope, fewer "we can't run this" responses
Regulatory Readiness	Methods developed with ICH M10 framework	Varies by CRO	Data suitable for IND-enabling studies

Representative ADME Demo Data

ADME metabolic stability data half-life intrinsic clearance

Metabolic stability data: half-life and intrinsic clearance across species

FAQ

Frequently Asked Questions

Q: What types of ADME/DMPK studies does Creative Proteomics offer?

We offer 11 sub-services organized by the ADME framework: metabolic stability (microsomes/S9/hepatocytes), drug permeability (Caco-2/PAMPA), plasma protein binding, tissue binding, LC-MS/MS bioanalysis for PK curves, metabolite identification (MetID), toxic metabolite detection, metabolic soft-spot analysis, drug-protein adduct MS, pharmaco-metabolomics, and pharmaco-proteomics. These can be ordered individually or as a customized ADME panel.

Q: What mass spectrometry platforms do you use for ADME studies?

We operate a multi-platform MS facility that includes triple quadrupole LC-MS/MS (for quantitative bioanalysis and routine ADME assays), high-resolution Orbitrap and Q-TOF systems (for metabolite identification, soft-spot analysis, and pharmaco-omics), and RapidFire MS (for high-throughput ADME screening). Platform selection is based on the specific requirements of each study.

Q: Do you follow regulatory guidelines for bioanalytical method validation?

Yes. For studies requiring regulatory-grade data, we develop and validate LC-MS/MS methods in accordance with ICH M10 guidelines. This includes full validation of calibration curves, accuracy, precision, selectivity, sensitivity, recovery, matrix effects, and stability.

Q: Can you handle reactive metabolite trapping and drug-protein adduct analysis?

Absolutely. We offer glutathione (GSH), cyanide, and other nucleophilic trapping agent experiments for reactive metabolite detection, analyzed by HRMS. For drug-protein adduct analysis, we provide covalent binding assessment using LC-MS/MS-based proteomics to identify modified proteins and residues.

Q: Do you offer integrated PK/PD interpretation or just raw data?

We deliver both. Every study includes a comprehensive report with raw data, processed data, QC summary, and calculated parameters. In addition, our scientists provide a scientific interpretation section that contextualizes the ADME data within your program's development stage — connecting in vitro clearance to predicted in vivo PK, or metabolite profiles to potential safety concerns.

Q: What sample types and quantities do you accept for ADME studies?

We accept a wide range of sample types including: compound powders or DMSO stocks (for in vitro assays), plasma/serum (for bioanalysis and protein binding), urine and bile (for excretion studies), and tissue homogenates (for distribution studies). Specific quantity requirements vary by assay — please refer to the Sample Requirements table above or contact our team for assay-specific guidance.

Q: Can I start with a single assay and expand later?

Yes. Our platform is designed for scalability. Many clients begin with a metabolic stability screen in human liver microsomes and subsequently expand to multi-species comparison, MetID, or a full ADME panel as their program advances. All assays share the same analytical platform, so data is consistent across the project lifecycle.

References

Cai H, Xing X, Su Y, Yang C. Innovative applications and future perspectives of chromatography-mass spectrometry in drug research. Frontiers in Pharmacology, 2025; 16:1529468.
Songvut P, Pholphana N, Suriyo T, et al. A validated LC-MS/MS method for clinical pharmacokinetics and presumptive phase II metabolic pathways following oral administration of Andrographis paniculata extract. Scientific Reports, 2023; 13:2534.
Marton A, Mohácsi Z, Decsi B, et al. High-throughput drug stability assessment via biomimetic metalloporphyrin-catalyzed reactions using laser-assisted rapid evaporative ionization mass spectrometry (LA-REIMS). Pharmaceutics, 2024; 16(10):1266.

Ready to Get Started?

Whether you need a single metabolic stability assay or a comprehensive ADME/DMPK panel spanning absorption to pharmaco-proteomics, the MassTarget platform is ready to support your program. Tell us about your compound and your development stage, and we'll design the right study plan.

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