Purpose: Methylsulfonylmethane (MSM) is an organosulfur phytochemical widely used as a dietary supplement with structure function claims including promotion of joint health. Untargeted metabolomics studies using nuclear magnetic resonance (NMR) have identified MSM in plasma and urine. However, NMR lacks the sensitivity of mass spectrometry (MS), which limits its application to pharmacokinetic studies designed to explore MSM’s concentration-effect relationship for purposes of establishing dosing guidelines. The purpose of this study was to develop an LC-MS method for determining MSM pharmacokinetics.
Methods: An HPLC-MS method using MSM and deuterated MSM (MSM-d6, internal standard) and liquid-liquid extraction was developed and validated in accordance with international guidelines. Human subjects (n =45) received chronic oral MSM administration (1, 2, or 3 grams daily) for 16 weeks.
Results: Calibration curves for MSM were linear over the concentration range of 5-1000 μM. The correlation coefficient for all assay was greater than 0.999 with weighting (1/x). The LLOQ for MSM was 5 μM. The range of inter- and intra-day accuracy and precision values in plasma were 1.3-13.7 % and 3.1-13.4%. Absolute recovery of MSM from plasma ranged from 90.6-101.6% using high, mid and low QC samples (5-1000 μM). Using the developed method, MSM pharmacokinetics were determined to be linear over a dose range of 1-3 grams daily.
Conclusion: The method proved well suited for determining MSM pharmacokinetics in humans. The availability of a robust LC-MS/MS method and MSM dose linearity data provide a framework for exploring MSM’s concentration-effect relationship to support various structure function claims.
Charles R. Yates– professor, Department of Pharmaceutical Sciences, University of Tennessee College of Pharmacy, Tennessee
Dejian Ma– Senior Research Specialist, Department of Pharmaceutical Sciences,University of Tennessee Health Science Center, Tennessee
Richard J. Bloomer– Dean, School of Health Studies & The Center for Wellness and Fitness, The University of Memphis, Tennessee
Matthew Butawan– Research Associate, School of Health Studies, The University of Memphis, Tennessee