LC—MS/MS method for quantification of atorvastatin, o-hydroxyatorvastatin, p-hydroxyatorvastatin, and atorvastatin lactone in rat plasma

Abstract

Summary.A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed for the quantification of atorvastatin, ortho-hydroxyatorvastatin, para-hydroxyatorvastatin, and atorvastatin lactone in rat plasma. Solid-phase extraction was used for preparation of samples. Rosuvastatin was chosen as an internal standard. Chromatographic separation was achieved on ZORBAX Eclipse C 18 Analytical, 4.6 × 100 mm (3.5 μm) column with a gradient mobile phase composed of acetonitrile and 0.1% acetic acid, at a flow rate of 400 μL min −1 . The column was kept at constant temperature (25 °C), and autosampler tray temperature was set at 4 °C. The following selected reaction monitoring (SRM) transitions were selected: (m/z, Q1 → Q3, collision energy) atorvastatin (559.47 → 440.03, 22 eV), atorvastatin lactone (541.36 → 448.02, 19 eV), orthohydroxyatorvastatin (575.20 → 440.18, 20 eV), para-hydroxyatorvastatin (575.54 → 440.18, 20 eV), and rosuvastatin (482.25 with selected combination of two fragments 257.77, 31 eV, and 299.81, 35 eV) in positive ion mode. The method was validated over a concentration range of 0.5-20 ng mL −1 for ortho-hydroxyatorvastatin and para-hydroxyatorvastatin and 0.1-20 ng mL −1 for atorvastatin and atorvastatin lactone with excellent linearity (r 2 ≥ 0.99). This method demonstrated acceptable precision and accuracy at four quality control concentration levels. The detection limits were 0.1 and 0.13 ng mL −1 for orthohydroxyatorvastatin and para-hydroxyatorvastatin, respectively, and 0.05 ng mL −1 for atorvastatin and atorvastatin lactone. All analytes were found to be stable at examined conditions. Validated method was applied for determination of atorvastatin and its metabolites in plasma of experimental animals.

New steps in acute coronary syndrome and antihyperlipidemic treatment: Determination of statins and metabolites by liquid chromatography tandem mass spectrometry

“…According to the method reported by El‐Bagary et al (2014), recovery values ranged between 75.07 and 77.83%, and CV values varied between 2.22 and 4.92% for atorvastatin. In the method developed by Crevar Sakač et al (2015), it was reported that the intra‐ and inter‐precision CV values for atorvastatin ranged from 7.56 to 14.56%. According to the method developed by Jani et al (2010), CV values for atorvastatin are reported to vary between 2 and 9.8%, while the recovery values vary between 50 and 68%.…”

Sensitive Spectrophotometric Determination of Atorvastatin in Pharmaceutical Formulation by Ion Pair Complexation with Pararosaniline Hydrochloride

“…Different techniques have been reported for the determination of ASN in pharmaceutical formulations and body fluids. These techniques involve HPLC with UV detection [2][3][4][5] , HPLC with fluorescence detection 6 , LC-MS/MS [7][8][9][10] , HPTLC [11][12][13] , voltametry [14][15][16] , capillary electrophoresis 17,18 , spectrophotometry [19][20][21] and spectrofluorometry 22 . Ion pair complexes or ion association complexes are complexes in which the species of analytical interest associates with oppositely charged ions to form a neutral extractable species 23 .…”