Interindividual variability in hepatic organic anion-transporting polypeptides and 1312 Salphati et al

Interindividual variability in protein expression of organic anion-transporting polypeptides (OATPs) OATP1B1, OATP1B3, OATP2B1, and multidrug resistance-linked P-glycoprotein (P-gp) or ABCB1 was quantified in frozen human livers (n = 64) and cryopreserved human hepatocytes (n = 12) by a validated liquid chromatography tandem mass spectroscopy (LC-MS/MS) method. Membrane isolation, sample workup, and LC-MS/MS analyses were as described before by our laboratory. Briefly, total native membrane proteins, isolated from the liver tissue and cryopreserved hepatocytes, were trypsin digested and quantified by LC-MS/MS using signature peptide(s) unique to each transporter. The mean 6 S.D. (maximum/minimum range in parentheses) protein expression (fmol/mg of membrane protein) in human liver tissue was OATP1B1- 2.0 6 0.9 (7), OATP1B3-1.1 6 0.5 (8), OATP2B1- 1 1.7 6 0.6 (5), and P-gp- 0.4 6 0.2 (8)