A One-Step Sample Processing Method in Combination with HPLC-MS/MS for the Simultaneous Quantification of Atorvastatin, Ezetimibe and Three Metabolites including <i>o</i>-Hydroxyl Atorvastatin, <i>p</i>-Hydroxyl Atorvastatin, and Ezetimibe-Glucuronide in Human Plasma
A simple and sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) method has been developed for the simultaneous determination of atorvastatin (ATOR), ezetimibe (EZM), and their three metabolites, including <i>o</i>-hydroxyl atorvastatin (<i>o</i>-OH ATOR), <...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | Separations |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2297-8739/10/7/409 |
| _version_ | 1827731762930778112 |
|---|---|
| author | T. Nguyen Nguyen Le Nai Ngoc Chuong Tuan Duc Nguyen |
| author_facet | T. Nguyen Nguyen Le Nai Ngoc Chuong Tuan Duc Nguyen |
| author_sort | T. Nguyen Nguyen Le |
| collection | DOAJ |
| description | A simple and sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) method has been developed for the simultaneous determination of atorvastatin (ATOR), ezetimibe (EZM), and their three metabolites, including <i>o</i>-hydroxyl atorvastatin (<i>o</i>-OH ATOR), <i>p</i>-hydroxyl atorvastatin (<i>p</i>-OH ATOR), and ezetimibe–glucuronide (EZM-G) in human plasma using benzyl paraben (BP) as the internal standard (IS). The analytes and IS were ionized using ESI positive ion mode (ATOR, <i>o</i>-OH ATOR, and <i>p</i>-OH ATOR), ESI negative ion mode (EZM, EZM-G, and BP), and operated in multiple reaction monitoring (MRM) mode. They were then extracted via salting-out assisted liquid–liquid extraction with acetonitrile and analyzed via liquid chromatography on a reversed-phase chromatographic column (50 mm × 4.6 mm; 3.5 µm) using a mixture of acetonitrile and an acetic acid solution (0.5%) as the mobile phase, showing high extraction efficiency (>70%), and a minimized matrix effect. The method was satisfactorily validated, and it showed excellent linearity over wide concentration ranges of 0.06–15 ng/mL, 0.6–150 ng/mL, 0.4–100 ng/mL, 0.12–30 ng/mL, and 0.05–3 ng/mL for EZM, EZM-G, ATOR, <i>o</i>-OH ATOR, and <i>p</i>-OH ATOR, respectively. |
| first_indexed | 2024-03-11T00:39:28Z |
| format | Article |
| id | doaj.art-c9f39c754abb4af8bc17c21acf56b967 |
| institution | Directory Open Access Journal |
| issn | 2297-8739 |
| language | English |
| last_indexed | 2024-03-11T00:39:28Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Separations |
| spelling | doaj.art-c9f39c754abb4af8bc17c21acf56b9672023-11-18T21:21:19ZengMDPI AGSeparations2297-87392023-07-0110740910.3390/separations10070409A One-Step Sample Processing Method in Combination with HPLC-MS/MS for the Simultaneous Quantification of Atorvastatin, Ezetimibe and Three Metabolites including <i>o</i>-Hydroxyl Atorvastatin, <i>p</i>-Hydroxyl Atorvastatin, and Ezetimibe-Glucuronide in Human PlasmaT. Nguyen Nguyen Le0Nai Ngoc Chuong1Tuan Duc Nguyen2BA/BE Test Center, Institute of Drug Quality Control Ho Chi Minh City, Ho Chi Minh City 700000, VietnamBA/BE Test Center, Institute of Drug Quality Control Ho Chi Minh City, Ho Chi Minh City 700000, VietnamFaculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 700000, VietnamA simple and sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) method has been developed for the simultaneous determination of atorvastatin (ATOR), ezetimibe (EZM), and their three metabolites, including <i>o</i>-hydroxyl atorvastatin (<i>o</i>-OH ATOR), <i>p</i>-hydroxyl atorvastatin (<i>p</i>-OH ATOR), and ezetimibe–glucuronide (EZM-G) in human plasma using benzyl paraben (BP) as the internal standard (IS). The analytes and IS were ionized using ESI positive ion mode (ATOR, <i>o</i>-OH ATOR, and <i>p</i>-OH ATOR), ESI negative ion mode (EZM, EZM-G, and BP), and operated in multiple reaction monitoring (MRM) mode. They were then extracted via salting-out assisted liquid–liquid extraction with acetonitrile and analyzed via liquid chromatography on a reversed-phase chromatographic column (50 mm × 4.6 mm; 3.5 µm) using a mixture of acetonitrile and an acetic acid solution (0.5%) as the mobile phase, showing high extraction efficiency (>70%), and a minimized matrix effect. The method was satisfactorily validated, and it showed excellent linearity over wide concentration ranges of 0.06–15 ng/mL, 0.6–150 ng/mL, 0.4–100 ng/mL, 0.12–30 ng/mL, and 0.05–3 ng/mL for EZM, EZM-G, ATOR, <i>o</i>-OH ATOR, and <i>p</i>-OH ATOR, respectively.https://www.mdpi.com/2297-8739/10/7/409atorvastatinezetimibe<i>o</i>-hydroxyl atorvastatin<i>p</i>-hydroxyl atorvastatinezetimibe–glucuronideLC-MS/MS |
| spellingShingle | T. Nguyen Nguyen Le Nai Ngoc Chuong Tuan Duc Nguyen A One-Step Sample Processing Method in Combination with HPLC-MS/MS for the Simultaneous Quantification of Atorvastatin, Ezetimibe and Three Metabolites including <i>o</i>-Hydroxyl Atorvastatin, <i>p</i>-Hydroxyl Atorvastatin, and Ezetimibe-Glucuronide in Human Plasma Separations atorvastatin ezetimibe <i>o</i>-hydroxyl atorvastatin <i>p</i>-hydroxyl atorvastatin ezetimibe–glucuronide LC-MS/MS |
| title | A One-Step Sample Processing Method in Combination with HPLC-MS/MS for the Simultaneous Quantification of Atorvastatin, Ezetimibe and Three Metabolites including <i>o</i>-Hydroxyl Atorvastatin, <i>p</i>-Hydroxyl Atorvastatin, and Ezetimibe-Glucuronide in Human Plasma |
| title_full | A One-Step Sample Processing Method in Combination with HPLC-MS/MS for the Simultaneous Quantification of Atorvastatin, Ezetimibe and Three Metabolites including <i>o</i>-Hydroxyl Atorvastatin, <i>p</i>-Hydroxyl Atorvastatin, and Ezetimibe-Glucuronide in Human Plasma |
| title_fullStr | A One-Step Sample Processing Method in Combination with HPLC-MS/MS for the Simultaneous Quantification of Atorvastatin, Ezetimibe and Three Metabolites including <i>o</i>-Hydroxyl Atorvastatin, <i>p</i>-Hydroxyl Atorvastatin, and Ezetimibe-Glucuronide in Human Plasma |
| title_full_unstemmed | A One-Step Sample Processing Method in Combination with HPLC-MS/MS for the Simultaneous Quantification of Atorvastatin, Ezetimibe and Three Metabolites including <i>o</i>-Hydroxyl Atorvastatin, <i>p</i>-Hydroxyl Atorvastatin, and Ezetimibe-Glucuronide in Human Plasma |
| title_short | A One-Step Sample Processing Method in Combination with HPLC-MS/MS for the Simultaneous Quantification of Atorvastatin, Ezetimibe and Three Metabolites including <i>o</i>-Hydroxyl Atorvastatin, <i>p</i>-Hydroxyl Atorvastatin, and Ezetimibe-Glucuronide in Human Plasma |
| title_sort | one step sample processing method in combination with hplc ms ms for the simultaneous quantification of atorvastatin ezetimibe and three metabolites including i o i hydroxyl atorvastatin i p i hydroxyl atorvastatin and ezetimibe glucuronide in human plasma |
| topic | atorvastatin ezetimibe <i>o</i>-hydroxyl atorvastatin <i>p</i>-hydroxyl atorvastatin ezetimibe–glucuronide LC-MS/MS |
| url | https://www.mdpi.com/2297-8739/10/7/409 |
| work_keys_str_mv | AT tnguyennguyenle aonestepsampleprocessingmethodincombinationwithhplcmsmsforthesimultaneousquantificationofatorvastatinezetimibeandthreemetabolitesincludingioihydroxylatorvastatinipihydroxylatorvastatinandezetimibeglucuronideinhumanplasma AT naingocchuong aonestepsampleprocessingmethodincombinationwithhplcmsmsforthesimultaneousquantificationofatorvastatinezetimibeandthreemetabolitesincludingioihydroxylatorvastatinipihydroxylatorvastatinandezetimibeglucuronideinhumanplasma AT tuanducnguyen aonestepsampleprocessingmethodincombinationwithhplcmsmsforthesimultaneousquantificationofatorvastatinezetimibeandthreemetabolitesincludingioihydroxylatorvastatinipihydroxylatorvastatinandezetimibeglucuronideinhumanplasma AT tnguyennguyenle onestepsampleprocessingmethodincombinationwithhplcmsmsforthesimultaneousquantificationofatorvastatinezetimibeandthreemetabolitesincludingioihydroxylatorvastatinipihydroxylatorvastatinandezetimibeglucuronideinhumanplasma AT naingocchuong onestepsampleprocessingmethodincombinationwithhplcmsmsforthesimultaneousquantificationofatorvastatinezetimibeandthreemetabolitesincludingioihydroxylatorvastatinipihydroxylatorvastatinandezetimibeglucuronideinhumanplasma AT tuanducnguyen onestepsampleprocessingmethodincombinationwithhplcmsmsforthesimultaneousquantificationofatorvastatinezetimibeandthreemetabolitesincludingioihydroxylatorvastatinipihydroxylatorvastatinandezetimibeglucuronideinhumanplasma |