Determination of drug-plasma protein binding using human serum albumin chromatographic column and multiple linear regression model

In vitro metabolism of specific CYP2D and CYP3A opioid substrates using rat liver S9 fractions and mass spectrometry reveal a severe metabolic impairment with increasing age

“…A linear regression (weighted 1/concentration) produced the best fit for the concentration–detector relationship. The regression model used was determined using the sum of the squares of the deviations (Beaudry, Coutu, & Brown, ). By convention, the regression line is considered to properly fit the calibration set when the sum of squares of the deviations is minimized.…”

Optimization of Sphingosine-1-phosphate-1 Receptor Agonists: Effects of Acidic, Basic, and Zwitterionic Chemotypes on Pharmacokinetic and Pharmacodynamic Profiles

“…Significant lymphocyte lowering was observed after a 3 mg/kg oral dose, and persisted over 48 h. PK sampling confirmed that this prolonged PD response was driven by high systemic levels of 8 (2.4 μM at the 48 h time point). The prolonged exposure is presumably a consequence of high plasma protein binding (HSA F ub 0.4%, based on chromatographic measurement), and possibly enterohepatic recirculation, a common feature of lipophilic acids …”

In vitro membrane binding and protein binding (IAM MB/PB technology) to estimate in vivo distribution: applications in early drug discovery

“…However, they have their limitations and are also very time-consuming. Biomimetic stationary phases have been validated by comparing the retention times obtained on the commercially available ChiralPak-HSA [37][38][39] and ChiralPak-AGP [40][41] stationary phases result in binding values that are proportional to the albumin and AGP binding of compounds obtained by equilibrium dialysis. When using biomimetic stationary phases the retention time of the compounds is directly proportional to the dynamic equilibrium constant between the mobile phase (buffer at physiological pH) and the actual body component (membrane and proteins) in the stationary phase.…”