Lanthionine and Other Relevant Sulfur Amino Acid Metabolites: Detection of Prospective Uremic Toxins in Serum by Multiple Reaction Monitoring Tandem Mass Spectrometry

Abstract

In the context of the vascular effects of hydrogen sulfide (H₂S), it is known that this gaseous endogenous biological modulator of inflammation, oxidative stress, etc. is a potent vasodilator. Chronic renal failure, a common disease affecting the aging population, is characterized by low levels of H₂S in plasma and tissues, which could mediate their typical hypertensive pattern, along with other abnormalities. Lanthionine and homolanthionine, natural non-proteinogenic amino acids, are formed as side products of H₂S production. Also in consideration of the intrinsic difficulties in H₂S measuring, these compounds have been proposed as reliable and stable markers of H₂S synthesis. However, in the setting of chronic renal failure patients on hemodialysis, they represent typical retention products (without ruling out the possibility of an increased intestinal synthesis) and prospective novel uremic toxins. Here, a method utilizing liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) in multiple reaction monitoring ion mode has been developed and evaluated for the determination of these key H₂S metabolites in plasma, by using a triple quadrupole mass spectrometer.