Carnosine is an endogenous dipeptide, composed of β-alanine and L-histidine, and is highly concentrated in skeletal muscle and other excitable tissues. Its physiological roles, based on its biochemical properties, include pH-buffering, metal-ion chelation and antioxidant capacity as well as the ability to protect against the formation of advanced glycation and lipoxidation end-products.1 For these reasons, besides its nutritional ergogenic application in the sport community,2 carnosine supplementation offers a therapeutic potential for the treatment of numerous diseases in which ischemic or oxidative stress is involved.1 Quantitation of carnosine in biological matrices appears to be crucial for these applications, and LC-MS procedures with isotope-labeled internal standards are the state-of-the-art approach for this analytical need.3 The use of these standards allows to account for variations during the complex sample preparation process, different matrix effects between patient samples, and variations in instrument performance. Figure 1 In this work, we present a fast and highly efficient synthetic route to obtain a deuterated carnosine analogue (Figure 1) starting from the trideuterated L-histidine (α-d1, imidazole-2,5-d2). Moreover, the use of Carnosine-d3 in the validation of a multiple reaction monitoring (MRM) LC-MS/MS method for the analytical quantitation of carnosine in a biological matrix will be reported. References 1. Boldyrev, A. A.; Aldini, G.; Derave, W. Physiol. Rev. 2013, 93, 1803–1845. 2. Brisola, G.; Zagatto, A. J. Strength Cond. Res. 2019, 33, 253-282. 3. Stokvis, E.; Rosing, H.; López-Lázaro, L.; Schellens, J. H. M.; Beijnen, J. H. Biomed. Chromatogr. 2004, 18, 400-402.

Synthesis and application of isotope-labeled carnosine in LCMS/MS / M. Maspero, E. Gilardoni, L. Regazzoni, G. Aldini, M. Carini, M. De Amici, C. Dallanoce. ((Intervento presentato al 26. convegno National Meeting in Medicinal Chemistry tenutosi a Milano nel 2019.

Synthesis and application of isotope-labeled carnosine in LCMS/MS

M. Maspero
Primo
;
E. Gilardoni
Secondo
;
L. Regazzoni;G. Aldini;M. Carini;M. De Amici
Penultimo
;
C. Dallanoce
Ultimo
2019

Abstract

Carnosine is an endogenous dipeptide, composed of β-alanine and L-histidine, and is highly concentrated in skeletal muscle and other excitable tissues. Its physiological roles, based on its biochemical properties, include pH-buffering, metal-ion chelation and antioxidant capacity as well as the ability to protect against the formation of advanced glycation and lipoxidation end-products.1 For these reasons, besides its nutritional ergogenic application in the sport community,2 carnosine supplementation offers a therapeutic potential for the treatment of numerous diseases in which ischemic or oxidative stress is involved.1 Quantitation of carnosine in biological matrices appears to be crucial for these applications, and LC-MS procedures with isotope-labeled internal standards are the state-of-the-art approach for this analytical need.3 The use of these standards allows to account for variations during the complex sample preparation process, different matrix effects between patient samples, and variations in instrument performance. Figure 1 In this work, we present a fast and highly efficient synthetic route to obtain a deuterated carnosine analogue (Figure 1) starting from the trideuterated L-histidine (α-d1, imidazole-2,5-d2). Moreover, the use of Carnosine-d3 in the validation of a multiple reaction monitoring (MRM) LC-MS/MS method for the analytical quantitation of carnosine in a biological matrix will be reported. References 1. Boldyrev, A. A.; Aldini, G.; Derave, W. Physiol. Rev. 2013, 93, 1803–1845. 2. Brisola, G.; Zagatto, A. J. Strength Cond. Res. 2019, 33, 253-282. 3. Stokvis, E.; Rosing, H.; López-Lázaro, L.; Schellens, J. H. M.; Beijnen, J. H. Biomed. Chromatogr. 2004, 18, 400-402.
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Synthesis and application of isotope-labeled carnosine in LCMS/MS / M. Maspero, E. Gilardoni, L. Regazzoni, G. Aldini, M. Carini, M. De Amici, C. Dallanoce. ((Intervento presentato al 26. convegno National Meeting in Medicinal Chemistry tenutosi a Milano nel 2019.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/688262
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