Atorvastatin lactone-d5 is intended for use as an internal standard for the quantification of atorvastatin lactone by GC- or LC-MS. Atorvastatin lactone is an active metabolite of the HMG-CoA reductase inhibitor atorvastatin.1,2 It is formed from atorvastatin by the UDP-glucuronosyltransferase (UGT) isoforms UGT1A3 and UGT1A1 in insect cell-derived supersomes expressing the human enzymes, and hydrolyzes to form atorvastatin in human serum at room temperature.2,3 Atorvastatin lactone inhibits HMG-CoA reductase (IC50 = 0.007 µM for the rat liver enzyme).1 It also inhibits the cytochrome P450 (CYP) isoforms CYP2C9.1 and CYP2C9.3 (IC50s = 16.8 and 5.62 µM, respectively), as well as P-glycoprotein (P-gp; IC50 = 3.1-5.2 µM).4,5
1.Roth, B.D., Blankley, C.J., Chucholowski, A.W., et al.Inhibitors of cholesterol biosynthesis. 3. Tetrahydro-4-hydroxy-6-[2-(1H-pyrrol-1-yl)ethyl]-2H-pyran-2-one inhibitors of HMG-CoA reductase. 2. Effects of introducing substituents at positions three and four of the pyrrole nucleusJ. Med. Chem.34(1)357-366(1990) 2.Schirris, T.J.J., Ritschel, T., Bilos, A., et al.Statin lactonization by uridine 5’-diphospho-glucuronosyltransferases (UGTs)Mol. Pharm.12(11)4048-4055(2015) 3.Jemal, M., Ouyang, Z., Chen, B.C., et al.Quantitation of the acid and lactone forms of atorvastatin and its biotransformation products in human serum by high-performance liquid chromatography with electrospray tandem mass spectrometryRapid Commun Mass Spectrom.13(11)1003-1015(1999) 4.Shiozawa, A., Yamaori, S., Kamijo, S., et al.Effects of acid and lactone forms of statins on S-warfarin 7-hydroxylation catalyzed by human liver microsomes and recombinant CYP2C9 variants (CYP2C9.1 and CYP2C9.3)Drug Metab. Pharmacokinet.36100364(2021) 5.Bogman, K., Peyer, A.-K., TÖrÖk, M., et al.HMG-CoA reductase inhibitors and P-glycoprotein modulationBr. J. Pharmacol.132(6)1183-1192(2001)