Analytical substrate: platforms, regimes, lifecycle, matrices.
The operational architecture beneath every method. Five analytical platforms · regulatory regimes · the four-phase method lifecycle · matrix types. The substrate iFeed is built on.
Analytical platforms.
5 instrument familiesThe analytical platform determines what's quantifiable, at what sensitivity, in what matrix. Choice of platform determines validation approach. Choice of platform determines regulatory expectations. The five families that cover the field today:
LC-MS/MS · triple quadrupole.
Workhorse for small molecules and peptides. SCIEX 5500/6500. Agilent 6470/6495. The default for PK/BE bioanalysis since the early 2000s.
HRAM · Orbitrap · Q-TOF.
High-resolution accurate-mass for biomarkers, peptides, identification work. Where LC-MS/MS leaves off and discovery-grade analysis begins.
HPLC-UV · PDA.
Older technology, limited sensitivity. Legacy methods that haven't migrated yet. Still seen in defined-impurity work and certain manufacturing contexts.
LBA · ligand-binding assays.
ELISA, MSD, immunoassays. Large molecules, biomarkers, biologics. The biopharma analytical staple where LC-MS struggles with sensitivity.
Hybrid LC-MS + IA.
Immunoaffinity capture + MS detection. The best-of-both for selected molecules — antibody-drug conjugates, low-abundance biomarkers.
Regulatory regimes.
BA-specific guidanceThe bioanalytical regulatory landscape harmonised globally on ICH M10 in January 2025. Each jurisdiction retains specific anchors. The complete comparison package:
Method lifecycle.
Development → retirementThe lifecycle is what regulators inspect. Each stage produces specific documentation; each stage has named acceptance criteria; each stage feeds the next. Skipping a stage is the most common cause of inspection observation in the bioanalytical world.
Development.
Method scoping, fit-for-purpose criteria, prototype runs. Selectivity, sensitivity, range exploration.
Validation.
Full validation per ICH M10 dimensions. Selectivity · accuracy · precision · linearity · stability · matrix effect.
Sample analysis.
Production runs. Incurred sample reanalysis. Calibration curve, QC performance per run. Real-time review.
Cross-validation.
Method-to-method, lab-to-lab, instrument-to-instrument when transfers occur. Bridging study design.
Retirement.
Method retirement protocol. Long-term stability close-out. Archive, traceability, succession to revised method.
Matrix types.
Where the analyte livesThe biological matrix dictates the validation approach. Plasma is the default; the others come with their own selectivity and stability questions, their own sample-collection complexity, their own regulator expectations.
Plasma.
K2-EDTA, lithium heparin. The default bioanalytical matrix. PK studies, BE studies, biomarker quantitation.
Whole blood.
Total drug exposure. Drugs that partition into red cells. Specific stability and haemolysis considerations.
Serum.
Clot-derived. Used for biomarkers, immunogenicity, certain biologics. Different matrix-effect profile from plasma.
Urine.
Excretion studies, mass balance, certain BE designs. pH and creatinine considerations.
Tissue.
Skin, brain, liver biopsy. Distribution studies. Homogenisation, recovery, normalisation.
CSF.
Cerebrospinal fluid. CNS drug distribution. Low-volume, high-stakes; compatibility with sensitive platforms.
Dried blood spot.
DBS — finger-prick collection. Pediatric, low-resource, decentralised trials. Specific haematocrit and recovery validation.
Saliva · other.
Therapeutic drug monitoring contexts. Free-fraction estimation. Specific to drug class and study purpose.