LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma
Апстракт
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 x 100 mm (3.5 mu m) column with a gradient mobile phase composed of acetonitrile and 0.1% acetic acid, at a flow rate of 400 mu L min(-1). The column was kept at constant temperature (25 degrees C), and autosampler tray temperature was set at 4 degrees C. The following selected reaction monitoring (SRM) transitions were selected: (m/z, Q1 - gt Q3, collision energy) atorvastatin (559.47 - gt 440.03, 22 eV), atorvastatin lactone (541.36 - gt 448.02, 19 eV), orthohydroxyatorvastatin (575.20 - gt 440.18, 20 eV), para-hydroxyatorvastatin (575.54 - gt 440.18, 20 eV), and rosuvastati...n (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) gt = 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.
Кључне речи:
atorvastatin / atherosclerosis / metabolites / LC-MS/MSИзвор:
Acta Chromatographica, 2016, 28, 3, 281-298Издавач:
- Akademiai Kiado Rt, Budapest
Финансирање / пројекти:
- Развој молекула са антиинфламаторним и кардиопроактивним дејством: структурне модификације, моделовање, физичкохемијска карактеризација и формулациона испитивања (RS-MESTD-Basic Research (BR or ON)-172041)
DOI: 10.1556/1326.2016.28.3.1
ISSN: 1233-2356
WoS: 000387843800002
Scopus: 2-s2.0-84989863847
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Crevar-Sakač, Milkica AU - Vujić, Zorica AU - Vujčić, Zoran AU - Marković, Bojan D. AU - Vasiljević, Dragana PY - 2016 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2349 AB - 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 x 100 mm (3.5 mu m) column with a gradient mobile phase composed of acetonitrile and 0.1% acetic acid, at a flow rate of 400 mu L min(-1). The column was kept at constant temperature (25 degrees C), and autosampler tray temperature was set at 4 degrees C. The following selected reaction monitoring (SRM) transitions were selected: (m/z, Q1 - gt Q3, collision energy) atorvastatin (559.47 - gt 440.03, 22 eV), atorvastatin lactone (541.36 - gt 448.02, 19 eV), orthohydroxyatorvastatin (575.20 - gt 440.18, 20 eV), para-hydroxyatorvastatin (575.54 - gt 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) gt = 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. PB - Akademiai Kiado Rt, Budapest T2 - Acta Chromatographica T1 - LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma VL - 28 IS - 3 SP - 281 EP - 298 DO - 10.1556/1326.2016.28.3.1 ER -
@article{ author = "Crevar-Sakač, Milkica and Vujić, Zorica and Vujčić, Zoran and Marković, Bojan D. and Vasiljević, Dragana", year = "2016", abstract = "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 x 100 mm (3.5 mu m) column with a gradient mobile phase composed of acetonitrile and 0.1% acetic acid, at a flow rate of 400 mu L min(-1). The column was kept at constant temperature (25 degrees C), and autosampler tray temperature was set at 4 degrees C. The following selected reaction monitoring (SRM) transitions were selected: (m/z, Q1 - gt Q3, collision energy) atorvastatin (559.47 - gt 440.03, 22 eV), atorvastatin lactone (541.36 - gt 448.02, 19 eV), orthohydroxyatorvastatin (575.20 - gt 440.18, 20 eV), para-hydroxyatorvastatin (575.54 - gt 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) gt = 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.", publisher = "Akademiai Kiado Rt, Budapest", journal = "Acta Chromatographica", title = "LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma", volume = "28", number = "3", pages = "281-298", doi = "10.1556/1326.2016.28.3.1" }
Crevar-Sakač, M., Vujić, Z., Vujčić, Z., Marković, B. D.,& Vasiljević, D.. (2016). LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma. in Acta Chromatographica Akademiai Kiado Rt, Budapest., 28(3), 281-298. https://doi.org/10.1556/1326.2016.28.3.1
Crevar-Sakač M, Vujić Z, Vujčić Z, Marković BD, Vasiljević D. LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma. in Acta Chromatographica. 2016;28(3):281-298. doi:10.1556/1326.2016.28.3.1 .
Crevar-Sakač, Milkica, Vujić, Zorica, Vujčić, Zoran, Marković, Bojan D., Vasiljević, Dragana, "LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma" in Acta Chromatographica, 28, no. 3 (2016):281-298, https://doi.org/10.1556/1326.2016.28.3.1 . .