title: Quantification of the N-desmethyl metabolite of rosuvastatin in human plasma by automated SPE followed by HPLC with tandem MS detection.
abstract: 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; 0.1M) soon after separation from red blood cells. N-Desmethyl rosuvastatin was stable in plasma:buffer at room temperature for 24h and at -70 degrees C for 12 months. The assay was applied successfully to the quantification of N-desmethyl rosuvastatin in human plasma following administration of rosuvastatin.
authors.affiliation: Quintiles Scotland Limited, Research Avenue South, Heriot-Watt University Research Park, Riccarton, Edinburgh EH14 4AP, UK. caroline.hull@quintiles.com
authors.forename: Caroline K
authors.initials: CK
authors.lastname: Hull
authors.forename: Paul D
authors.initials: PD
authors.lastname: Martin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Warwick
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thomas
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D005464:Fluorobenzenes / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D011743:Pyrimidines / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D000068718:Rosuvastatin Calcium; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013449:Sulfonamides / Q000097:blood* / Q000737:chemistry / Q000378:metabolism
chemical_list: D005464:Fluorobenzenes; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium