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Updated: Feb 22, 2026

High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry
Published on: April 23, 2019
Evaluation of the potential use of hybrid LC-MS/MS for active drug quantification applying the 'free analyte QC
Gregor Jordan1, Ichio Onami2, Julia Heinrich1
1Roche Pharma Research & Early Development (pRED), Pharmaceutical Sciences, Global DMPK & Bioanalytical R&D, Roche Innovation Center Munich, Nonnenwald 2, 82377 Penzberg, Germany.
Aim:
Assessment of active drug exposure of biologics may be crucial for drug development. Typically, ligand-binding assay methods are used to provide free/active drug concentrations. To what extent hybrid LC-MS/MS procedures enable correct 'active' drug quantification is currently under consideration. Experimental & results: The relevance of appropriate extraction condition was evaluated by a hybrid target capture immuno-affinity LC-MS/MS method using total and free/active quality controls (QCs). The rapid extraction (10 min) provided correct results, whereas overnight incubation resulted in significant overestimation of the free/active drug (monclonal antibody) concentration. Conventional total QCs were inappropriate to determine optimal method conditions in contrast to free/active QCs.
Conclusion:
The 'free/active analyte QC concept' enables development of appropriate extraction conditions for correct active drug quantification by hybrid LC-MS/MS.
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