Measurements of blood DMSO and DMSO₂ in a healthy person and a hemodialysis patient

Abstract

Background. The aim of the present study was twofold: (1) to confirm gas chromatography/mass spectrometry (GS/MS) as a means of measuring blood and urine concentrations of dimethyl sulfoxide (DMSO) and its metabolite, dimethyl sulfone (DMSO₂), and (2) to measure blood concentrations of DMSO and DMSO₂ in a hemodialysis (HD) patient receiving DMSO.

Methods. Measurements were made after deprotenization, using 450 μl of plasma or urine, then using 2 μl of supernatant for GC/MS. DMSO-d ₆ was used as the internal standard. The two subjects were a healthy 43-year-old man, weighing 82 kg, who received a single dose of 5 ml DMSO, and a 48-year-old man, an HD patient, weighing 56 kg, with a 3-year history of HD. The etiology of chronic renal failure was primary amyloidosis. The HD patient had been receiving 5 ml DMSO/day for 3 years and 10 months.

Results. A good calibration curve for trace amounts of DMSO and DMSO₂, in the range of 0.25 ng to 50 ng, was obtained from GC/MS. The recovery rate and repeatability from plasma were also good. In the healthy subject, the maximum drug concentration time (Tmax) for DMSO was 2.0 h, the maximum drug concentration (Cmax), 74.92 μg/ml whole blood, and T1/2, 6.8 h. Tmax for DMSO₂ was 24.0 h, Cmax, 58.32 μg/ml whole blood, and T1/2 was greatly extended, to 56.8 h. Blood concentrations of DMSO and DMSO₂ in the HD patient before HD were remarkably high, at 171.32 and 814.22 μg/ml whole blood, respectively. After HD, these values decreased to 66.48 and 405.05 μg/ml whole blood, respectively, but were still higher than the value in the healthy subject.

Conclusions. Because the effective drug concentration of DMSO has not been established, the dose level for HD patients must be investigated from the standpoint of therapeutic drug monitoring. Furthermore, as the blood concentration of the metabolite DMSO₂ is higher than that of DMSO, attention must be directed to the pharmacokinetics of DMSO₂.