Quantification of the N-desmethyl metabolite of rosuvastatin in human plasma by automated SPE followed by HPLC with tandem MS detection

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 35; no. 3; pp. 609 - 614
• Main Authors: Hull, Caroline K, Martin, Paul D, Warwick, Michael J, Thomas, Elizabeth
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28.05.2004; Elsevier Science
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Drug Stability; Fluorobenzenes - blood; Fluorobenzenes - chemistry; Fluorobenzenes - metabolism; Fundamental and applied biological sciences. Psychology; Gas Chromatography-Mass Spectrometry; General pharmacology; HMG-CoA reductase inhibitor; HPLC-MS/MS; Humans; Medical sciences; N-desmethyl rosuvastatin; Pharmacology. Drug treatments; Pyrimidines - blood; Pyrimidines - chemistry; Pyrimidines - metabolism; Rosuvastatin; Rosuvastatin Calcium; SPE; Spectrometry, Mass, Electrospray Ionization - methods; Sulfonamides - blood; Sulfonamides - chemistry; Sulfonamides - metabolism; SPE; Rosuvastatin; HPLC-MS/MS; N-desmethyl rosuvastatin; HMG-CoA reductase inhibitor; Human; Solid phase extraction; Biological fluid; Temperature; Enzyme; Metabolite; Enzyme inhibitor; HPLC chromatography; Red blood cell; Statin derivative; Electrospray; Coenzyme; Blood plasma; SPE: N-desmethyl rosuvastatin; Blood cell; Investigation method; Sodium; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Antilipemic agent
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2003.12.022

A selective, accurate and precise assay was developed for the quantification in human plasma of the N-desmethyl metabolite of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor rosuvastatin. The assay—employing automated SPE followed by HPLC with positive ion electrospray tandem MS (HPLC-MS/MS)—was validated. The standard curve range for N-desmethyl rosuvastatin in human plasma was 0.5–30 ng/ml with 0.5 ng/ml being the limit of quantification. Plasma samples were mixed 1:1 with sodium acetate buffer (pH 4.0; 0.1 M) soon after separation from red blood cells. N-Desmethyl rosuvastatin was stable in plasma:buffer at room temperature for 24 h and at −70 °C for 12 months. The assay was applied successfully to the quantification of N-desmethyl rosuvastatin in human plasma following administration of rosuvastatin.