Fluvastatin

Molecular formula: C24H26FNO4 Molecular weight: 410.5 CAS Registry No.: 93957-55-2 (fluvastatin sodium)

SAMPLE Matrix: blood Sample preparation: Dilute with an equal volume of water, precipitate with two 10 mL portions of acetone:MeOH 5:2, collect the supernatant, reduce it in volume, inject an aliquot. HPLC VARIABLES Column: 300 X 3.9 10 |xm fatty acid (Waters) Mobile phase: Gradient. Buffer:MeOH 100:0 for 2 min, to 72:18 over 25 min, maintain at 72:28 for 18 min, to 62:38 over 19 min, maintain at 62:38 for 6 min, to 59.7:40.3 over 4 min, to 59.2:40.8 over 2 min, maintain at 59.2:40.8 for 2 min, to 58:42 over 2 min, maintain at 58:42 for 2 min, to 54:46 over 4 min, to 45:55 over 4 min, maintain at 45: 55 for 2 min, to 20:80 over 6 min, maintain at 20:80 over 6 min, return to initial conditions over 4 min. Flow rate: 1 Detector: UV 254 CHROMATOGRAM Retention time: 85 OTHER SUBSTANCES Extracted: metabolites KEYWORDS plasma; human; rat; hamster REFERENCE
Dain, J.G.; Fu, E.; Gorski, J.; Nicoletti, J.; Scallen, T.J. Biotransformation of fluvastatin sodium in humans. Drug Metab.Dispos., 1993, 22, 567-572

SAMPLE Matrix: blood Sample preparation: 1 mL Plasma + 1 mL MeCN, mix on a Maxi-Mix for 5 s, add 1 mL 300 ng/mL IS in water, add 2 mL phosphate buffer, add 10 mL MTBE, shake horizontally on a platform shaker at 200 cycles/min for 15 min, centrifuge at 700 g for 5 min. Remove the upper organic layer and evaporate it to dryness under vacuum, reconstitute the residue in 400 jxL mobile phase, inject a 200 |xL aliquot. HPLC VARIABLES Column: 150 X 4.6 5 jjim Supelcosil LC-18 Mobile phase: MeOH: 13 mM tetrabutylammonium fluoride 60:40 Column temperature: 50 Injection volume: 200

Detector: F ex 305 em 380 CHROMATOGRAM Retention time: 9.2 Internal standard: ([R*, S*)-(E)-]()-7-[3-(4-fluorophenyl)-l-(l-methylethyl)-lH-indol-2yl]-3,5-dihydroxy-6-methyl-6-heptenoic acid, monosodium salt (Sandoz 63-267, 6-methylfluvastatin) (12.8) Limit of quantitation: 1 ng/mL KEYWORDS plasma; protect from light; pharmacokinetics REFERENCE
Kalafsky, G.; Smith, H.T.; Choc, M.G. High-performance liquid chromatographic method for the determination of fluvastatin in human plasma. J.Chromatogr., 1993, 614, 307-313

SAMPLE Matrix: blood Sample preparation: Adjust pH of 500 jxL blood to 7, extract with MTBE. Remove the organic layer and evaporate it to dryness, reconstitute the residue in mobile phase, inject an aliquot. HPLCVARIABLES Column: 150 X 4.6 5 jim Supelcosil LC-18 Mobile phase: MeOH: water 60:40 containing 5 mL/L tetrabutylammonium fluoride Column temperature: 50 Detector: F ex 305 em 380 CHROMATOGRAM Internal standard: sodium 3,5-dihydroxy-7-[3-(4-fluorophenyl)-l-(l-methylethyl)-lH-indole-2-yl]-6-methylhept-6-enoate Limit of detection: 1 ng/mL KEYWORDS pharmacokinetics; rabbit REFERENCE
Tse, RL.; Labbadia, D. Absorption and disposition of fluvastatin, an inhibitor of HMG-CoA reductase, in the rabbit. Biopharm.Drug Dispos., 1992, 13, 285-294

SAMPLE Matrix: blood Sample preparation: Adjust pH of 500 |xL blood to 7, extract with MTBE. Remove the organic layer and evaporate it to dryness, reconstitute the residue in MeCN: 5 mM pH 6.5 hexyltriethylammonium phosphate 5:95, inject an aliquot. HPLC VARIABLES Column: C8 Mobile phase: MeCN: 5 mM pH 6.5 hexyltriethylammonium phosphate 40:60 Column temperature: 50 Detector: F ex 305 em 380 CHROMATOGRAM Limit of detection: 2 ng/mL

KEYWORDS pharmacokinetics; mouse; dog; monkey REFERENCE Tse, F.L.; Smith, H.T.; Ballard, RH.; Nicoletti, J. Disposition of fluvastatin, an inhibitor of HMG-CoA reductase, in mouse, rat, dog, and monkey. Biopharm.Drug Dispos., 1990, 11, 519-531