Confirmation of Statin and Fibrate Use from Small-Volume Archived Plasma Samples by High-Throughput LC-MS/MS Method

• Published in: International journal of molecular sciences Vol. 24; no. 9; p. 7931
• Main Authors: Kusovschi, Jennifer D, Ivanova, Anna A, Gardner, Michael S, McGarrah, 3rd, Robert W, Kraus, William E, Kuklenyik, Zsuzsanna, Pirkle, James L, Barr, John R
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.04.2023; MDPI
• Subjects: Archives & records; Atherosclerosis; Atorvastatin; Atorvastatin - therapeutic use; Biomarkers; Cardiac patients; Cardiovascular agents; Cardiovascular disease; Cholesterol; Chromatography; Chromatography, Liquid; Drugs; Fenofibrate; fibrates; Fibric Acids - therapeutic use; human plasma; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; LC-MS/MS; Lipid metabolism; Lipids; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Medical records; Metabolites; Methods; Patient compliance; Physiological aspects; Plasma; Population studies; Solvents; Statins; Tandem Mass Spectrometry; Triglycerides; Canada; Massachusetts; LC-MS/MS; cardiovascular disease; fibrates; statins; mass spectrometry; medical records; human plasma
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24097931

Designing studies for lipid-metabolism-related biomarker discovery is challenging because of the high prevalence of various statin and fibrate usage for lipid-lowering therapies. When the statin and fibrate use is determined based on self-reports, patient adherence to the prescribed statin dose regimen remains unknown. A potentially more accurate way to verify a patient's medication adherence is by direct analytical measurements. Current analytical methods are prohibitive because of the limited panel of drugs per test and large sample volume requirement that is not available from archived samples. A 4-min-long method was developed for the detection of seven statins and three fibrates using 10 µL of plasma analyzed via reverse-phase liquid chromatography and tandem mass spectrometry. The method was applied to the analysis of 941 archived plasma samples collected from patients before cardiac catheterization. When statin use was self-reported, statins were detected in 78.6% of the samples. In the case of self-reported atorvastatin use, the agreement with detection was 90.2%. However, when no statin use was reported, 42.4% of the samples had detectable levels of statins, with a similar range of concentrations as the samples from the self-reported statin users. The method is highly applicable in population studies designed for biomarker discovery or diet and lifestyle intervention studies, where the accuracy of statin or fibrate use may strongly affect the statistical evaluation of the biomarker data.