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Simultaneous LC-MS/MS analysis of simvastatin, atorvastatin, rosuvastatin and their active metabolites for plasma samples of obese patients underwent gastric bypass surgery.
J Pharm Biomed Anal 2019; 164:258-267JP

Abstract

Statins, HMG-CoA reductase inhibitors, are considered the first line treatment of hyperlipidemia to reduce the risk of atherosclerotic cardiovascular diseases. The prevalence of hyperlipidemia and the risk of atherosclerotic cardiovascular diseases are higher in obese patients. Published methods for the quantification of statins and their active metabolites did not test for matrix effect of or validate the method in hyperlipidemic plasma. A sensitive, specific, accurate, and reliable LC-MS/MS method for the simultaneous quantification of simvastatin (SMV), active metabolite of simvastatin acid (SMV-A), atorvastatin (ATV), active metabolites of 2-hydroxy atorvastatin (2-OH-ATV), 4-hydroxy atorvastatin (4-OH-ATV), and rosuvastatin (RSV) was developed and validated in plasma with low (52-103 mg/dl, <300 mg/dl) and high (352-403 mg/dl, >300 mg/dl) levels of triglyceride. The column used in this method was ACQUITY UPLC BEH C18 column (2.1 × 100 mm I.D., 1.7 μm). A gradient elution of mobile phase A (10 mM ammonium formate and 0.04% formic acid in water) and mobile phase B (acetonitrile) was used with a flow rate of 0.4 ml/min and run time of 5 min. The transitions of m/z 436.3 → 285.2 for SMV, m/z 437.2 → 303.2 for SMV-A, m/z 559.2 → 440.3 for ATV, m/z 575.4 → 440.3 for 2-OH-ATV and 4-OH-ATV, m/z 482.3 → 258.1 for RSV, and m/z 412.3 → 224.2 for fluvastatin (internal standard, IS) were determined by Selected Reaction Monitoring (SRM) method to detect transitions ions in the positive ion mode. The assay has a linear range of 0.25 (LLOQ) -100 ng/ml for all six analytes. Accuracy (87-114%), precision (3-13%), matrix effect (92-110%), and extraction recovery (88-100%) of the assay were within the 15% acceptable limit of FDA Guidelines in variations for plasma with both low and high triglyceride levels. The method was used successfully for the quantification of SMV, ATV, RSV, and their active metabolites in human plasma samples collected for an ongoing clinical pharmacokinetic and pharmacodynamic study on patients prior to and post gastric bypass surgery (GBS).

Authors+Show Affiliations

Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, United States. Electronic address: amel-zailik@uh.edu.Department of Pharmacy Practice and Clinical Health Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, United States.Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, United States.Department of Surgery, Houston Methodist Hospital, Houston, TX, United States.Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, United States.

Pub Type(s)

Journal Article
Validation Studies

Language

eng

PubMed ID

30396053

Citation

El-Zailik, Asma, et al. "Simultaneous LC-MS/MS Analysis of Simvastatin, Atorvastatin, Rosuvastatin and Their Active Metabolites for Plasma Samples of Obese Patients Underwent Gastric Bypass Surgery." Journal of Pharmaceutical and Biomedical Analysis, vol. 164, 2019, pp. 258-267.
El-Zailik A, Cheung LK, Wang Y, et al. Simultaneous LC-MS/MS analysis of simvastatin, atorvastatin, rosuvastatin and their active metabolites for plasma samples of obese patients underwent gastric bypass surgery. J Pharm Biomed Anal. 2019;164:258-267.
El-Zailik, A., Cheung, L. K., Wang, Y., Sherman, V., & Chow, D. S. (2019). Simultaneous LC-MS/MS analysis of simvastatin, atorvastatin, rosuvastatin and their active metabolites for plasma samples of obese patients underwent gastric bypass surgery. Journal of Pharmaceutical and Biomedical Analysis, 164, pp. 258-267. doi:10.1016/j.jpba.2018.10.045.
El-Zailik A, et al. Simultaneous LC-MS/MS Analysis of Simvastatin, Atorvastatin, Rosuvastatin and Their Active Metabolites for Plasma Samples of Obese Patients Underwent Gastric Bypass Surgery. J Pharm Biomed Anal. 2019 Feb 5;164:258-267. PubMed PMID: 30396053.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simultaneous LC-MS/MS analysis of simvastatin, atorvastatin, rosuvastatin and their active metabolites for plasma samples of obese patients underwent gastric bypass surgery. AU - El-Zailik,Asma, AU - Cheung,Lily K, AU - Wang,Yang, AU - Sherman,Vadim, AU - Chow,Diana S-L, Y1 - 2018/10/28/ PY - 2018/08/03/received PY - 2018/10/25/accepted PY - 2020/02/05/pmc-release PY - 2018/11/6/pubmed PY - 2019/3/20/medline PY - 2018/11/6/entrez KW - Atorvastatin and metabolites KW - Hyperlipidemic plasma KW - LC–MS/MS KW - Obese subjects from GBS KW - Rosuvastatin KW - Simvastatin and metabolite SP - 258 EP - 267 JF - Journal of pharmaceutical and biomedical analysis JO - J Pharm Biomed Anal VL - 164 N2 - Statins, HMG-CoA reductase inhibitors, are considered the first line treatment of hyperlipidemia to reduce the risk of atherosclerotic cardiovascular diseases. The prevalence of hyperlipidemia and the risk of atherosclerotic cardiovascular diseases are higher in obese patients. Published methods for the quantification of statins and their active metabolites did not test for matrix effect of or validate the method in hyperlipidemic plasma. A sensitive, specific, accurate, and reliable LC-MS/MS method for the simultaneous quantification of simvastatin (SMV), active metabolite of simvastatin acid (SMV-A), atorvastatin (ATV), active metabolites of 2-hydroxy atorvastatin (2-OH-ATV), 4-hydroxy atorvastatin (4-OH-ATV), and rosuvastatin (RSV) was developed and validated in plasma with low (52-103 mg/dl, <300 mg/dl) and high (352-403 mg/dl, >300 mg/dl) levels of triglyceride. The column used in this method was ACQUITY UPLC BEH C18 column (2.1 × 100 mm I.D., 1.7 μm). A gradient elution of mobile phase A (10 mM ammonium formate and 0.04% formic acid in water) and mobile phase B (acetonitrile) was used with a flow rate of 0.4 ml/min and run time of 5 min. The transitions of m/z 436.3 → 285.2 for SMV, m/z 437.2 → 303.2 for SMV-A, m/z 559.2 → 440.3 for ATV, m/z 575.4 → 440.3 for 2-OH-ATV and 4-OH-ATV, m/z 482.3 → 258.1 for RSV, and m/z 412.3 → 224.2 for fluvastatin (internal standard, IS) were determined by Selected Reaction Monitoring (SRM) method to detect transitions ions in the positive ion mode. The assay has a linear range of 0.25 (LLOQ) -100 ng/ml for all six analytes. Accuracy (87-114%), precision (3-13%), matrix effect (92-110%), and extraction recovery (88-100%) of the assay were within the 15% acceptable limit of FDA Guidelines in variations for plasma with both low and high triglyceride levels. The method was used successfully for the quantification of SMV, ATV, RSV, and their active metabolites in human plasma samples collected for an ongoing clinical pharmacokinetic and pharmacodynamic study on patients prior to and post gastric bypass surgery (GBS). SN - 1873-264X UR - https://www.unboundmedicine.com/medline/citation/30396053/Simultaneous_LC_MS/MS_analysis_of_simvastatin_atorvastatin_rosuvastatin_and_their_active_metabolites_for_plasma_samples_of_obese_patients_underwent_gastric_bypass_surgery_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0731-7085(18)31800-4 DB - PRIME DP - Unbound Medicine ER -