Recent advances in mass spectrometric and other analytical techniques for the identification of drug metabolites

A Review of Advances in Bioanalytical Methods for the Detection and Quantification of Olanzapine and Its Metabolites in Complex Biological Matrices

“…Adding a solvent such as acetonitrile or methanol lowers the dielectric constant of the protein-containing solution, which increases the attraction between charged particles and facilitates their electrostatic interaction. This leads to the displacement of water from the hydrophobic surface area of the proteins, which in turn leads to the breaking of the hydrophobic interactions between them, thus causing the proteins to precipitate out of the solution ( Figure 4 ) [ 24 ]. Y. Cao et al (2020) proposed a basic procedure for sample preparation by protein precipitation.…”

“…Based on the difference in matrix components, increases the attraction between charged particles and facilitates their electrostatic interaction. This leads to the displacement of water from the hydrophobic surface area of the proteins, which in turn leads to the breaking of the hydrophobic interactions between them, thus causing the proteins to precipitate out of the solution (Figure 4) [24]. Y.…”

Defining Blood Plasma and Serum Metabolome by GC-MS

“…Precipitation is accomplished by changing the pH and polarity of the solution. As a result, intramolecular interactions are disrupted, the protein denatures, aggregates, and falls out of solution [71,72]. For plasma and serum, the excess amounts of organic solvents such as methanol or acetonitrile [72,73] are used, followed by high-speed centrifugation and separation of the supernatant (Figure 3, stage 2).…”

Radiolabel Uncovers Nonintuitive Metabolites of BIIB104: Novel Release of [14C]Cyanide from 2-Cyanothiophene and Subsequent Formation of [14C]Thiocyanate

“…Advancements over recent decades in liquid chromatography -high-resolution mass spectrometry (LC-HRMS) and associated computer algorithms have made LC-HRMS-based metabolite identification highly efficient for most cases (Castro-Perez and Prakash, 2020;Ma and Chowdhury, 2011;Schadt et al, 2018). Consequently, radiolabeled drug-metabolism studies (with 14 C or 3 H) are now backloaded in drug development, with human radiolabeled absorption, distribution, metabolism and excretion (ADME) studies often occurring in parallel to Phase II or III studies (Schadt et al, 2018).…”