Determination of Fluvastatin Concentrations in Human Plasma by RP-HPLC with Fluorescence Detector and Its Application to Pharmacokinetic Study
Zourong Ruan · Zhōnghuá yàoxué zázhì · 2006
OBJECTIVE To establish a RP-HPLC for the determination of fluvastatin(FV) concentrations in human plasma.METHODS Plasma samples (100 μL) were deproteinized by precipitation with acetonitrile (containing 0.2% phosphoric acid), centrifuged and the supernatant was directly injected into HPLC. Separation was achieved on a reverse phase column (Kromasil C_ 18 ODS 4.6 mm×150 mm,5 μm), with a mixture of 0.02 mol·L -1 monobasic potassium phosphate-acetonitrile (53∶47) as mobile phase. The flow rate was 1.2 mL·min -1 .The fluorescence detector was set at excitation wavelength of 274 nm and emission wavelength of 450 nm. The external standard method was used to quantify FV. The assay was validated and applicated to pharmacokinetic study of FV in 20 healthy volunteers following a single oral dose of 40 mg Lescol D○R .RESULTS Endogenous chemicals and metabolite did not interfere with FV. The calibration curves were linear in the range of 2～600 μg·L -1 (r=0.999 999,n=6), with a limit of quantitation of 2 μg·L -1 . The within-and between-day RSDs of quality-control samples at high-, medium-and low-concentrations were less than 8%. The average method recovery was in the range of 95.0%～100.9%. The average absolute recovery was 111.4%. The plasma concentration-time curves indicated great individual variability of FV disposition in Chinese. Major pharmacokinetic parameters included ρ_ max (491.4±211.4)μg·L -1 , t_ max (0.6±0.2)h,t_ 1/2 (1.1±0.3) h and AUC_ 0～t (540.2±226.5)μg·h·L -1 .CONCLUSION The is stable, simple, rapid, accurate, sensitive and applicable for determining plasma concentrations of fluvastatin in its pharmacokinetic studies. Compared with caucasians, Chinese volunteers show higher values of ρ_ max ,AUC_ 0～t ,rapid absorption and terminal elimination profile.