Determination of Rosuvastatin and its Metabolite N-Desmethyl Rosuvastatin in Human Plasma by Liquid Chromatography-High Resolution Mass Spectrometry: Method Development, Validation, and Application to Pharmacokinetic Study

作者：Shah Yasar; Iqbal Zafar^*; Ahmad Lateef; Nazir Shabnam; Watson David G; Khuda Fazli; Khan Abad; Khan Muhammad Imran; Khan Abbas; Nasir Fazli

来源：Journal of Liquid Chromatography & Related Technologies, 2015, 38(8): 863-873.

DOI：10.1080/10826076.2014.982866

• rosuvastatin
• pharmacokinetics
• validation
• LC-MS/MS
• N-desmethyl rosuvastatin
• human plasma

A novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of rosuvastatin (rosuva) and its metabolite N-desmethyl rosuvastatin (NDM-rosuva) in human plasma using atorvastatin as internal standard. The method was validated according to international guidelines. The analytical column used was HiChrom((R)) C18 (150x3.0mm, 3 mu m; Reading, UK) and the mobile phase comprised of 0.1% formic acid in acetonitrile and 0.1% formic acid in water (70:30v/v), pumped at 300 mu L/min. The precipitation of plasma proteins and extraction of analytes were carried out by a simple one-step procedure using acetonitrile. The calibration curves were linear (r(2)=0.999) over the concentration range of 0.2-20ng/mL for rosuva and 0.1-10ng/mL for NDM-rosuva. The lower limits of detection and quantification for rosuva were 0.1 and 0.2ng/mL, whereas for NDM-rosuva, these were 0.03 and 0.1ng/mL, respectively. The intra- and inter-day precisions expressed as relative standard deviations (RSDs) were less than 2.5%. The average absolute recoveries of both rosuva and NDM-rosuva were greater than 95%. The method was successfully applied for the determination of rosuva and NDM-rosuva pharmacokinetics and drug-drug interaction studies.

• 出版日期2015-5-9