74th ASMS Conference on Mass Spectrometry and Allied Topics

Compared with traditional delivery systems, metal nanoparticles (MNPs), including magnetic iron oxide NPs, nanocrystalline silver, gold NPs, platinum NPs, and manganese dioxide NPs, offer significant advantages such as enhanced stability, prolonged circulation time, improved distribution, and precise targeting capability. MNPs exhibit remarkable versatility in surface modification, enabling customization for diverse biomedical applications. By conjugating functional groups (e.g., polymers, peptides, or targeting ligands) to their surfaces, MNPs can achieve site-specific drug delivery.

Improved pretreatment methods for the elimination of ADC-related interferences are introduced in the study, which were applied for the detection of free payloads including MMAE, DXD, Exatecan, and Payload 1.

Consequently, sample preparation typically relies on liquid-liquid extraction (LLE) or solid-phase extraction (SPE). LLE offers operational simplicity and low cost but is prone to pronounced matrix effects, particularly in tissue homogenates and excretory matrices (e.g., urine, bile). In contrast, SPE provides broad applicability across diverse biological matrices yet involves greater operational complexity and higher cost. Herein, we developed a new sample pretreatment method of magnetic-solid phase extraction (mSPE), which offered advantages over LLE and SPE in terms of sample cleanliness, operational simplicity, and cost-effectiveness.

Covalent inhibitors are small molecules that bind to target proteins via covalent bonds, enhancing inhibitory activity. They are classified as reversible or irreversible inhibitors based on bond type. Voxelotor, a sickle cell disease inhibitor, uses its aldehyde group to reversibly form a Schiff base with Val1 amino group on hemoglobin's beta chain. This stabilizes hemoglobin's R-state via intramolecular hydrogen bonds, boosting oxygen affinity. Optimized pretreatment overcomes extremely low extraction recovery of Schiff-Base forming reversible covalent compounds in whole blood.