Determination of rosuvastatin at picogram level in serum by fluorimetric derivatization with 9-anthryldiazomethane using HPLC.
For the first time, a carboxyl group derivatization assay has been developed and validated for the determination of the cholesterol-lowering drug rosuvastatin in human serum at picogram level by high-performance liquid chromatography with fluorescence detection. The assay procedure involved a simple one-step liquid-liquid extraction of rosuvastatin with lovastatin as internal standard from serum with an ethyl acetate-methyl tertiary buthyl ether (1:1) mixture. After pre-column derivatization with 9-anthryldiazomethane at room temperature for one hour, the reaction mixture was injected onto a Phenomenex, Synergi C18 column (250 × 4.6 mm, 4 µ i.d.). The analytes were separated with a mobile phase composed of acetonitrile-water in gradient elution mode and detected at λ(em) = 410 nm, exciting at 366 nm. Calibration curves were constructed in concentration range of 0.01-20.0 ng/mL and limit of detection and limit of quantification values were found to be 0.68 and 2.30 pg/mL, respectively. To test suitability of the developed methods for clinic use, the pharmacokinetics of rosuvastatin were investigated after oral administration of a 20 mg rosuvastatin film tablet to a healthy volunteer and maximum plasma concentration, time to reach that concentration and elimination half life were found to be 17.5 ng/mL, 3.5 h and 18.09 h, respectively.
Istanbul University, Faculty of Pharmacy, Department of Analytical Chemistry, 34116, Beyazit, Istanbul - Turkey. senacaglar@yahoo.com
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D000328:Adult; D000873:Anthracenes / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry*; D005464:Fluorobenzenes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D011743:Pyrimidines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D000068718:Rosuvastatin Calcium; D013050:Spectrometry, Fluorescence; D013449:Sulfonamides / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
D000873:Anthracenes; D005456:Fluorescent Dyes; D005464:Fluorobenzenes; D011743:Pyrimidines; D013449:Sulfonamides; C027347:9-diazomethylanthracene; D000068718:Rosuvastatin Calcium