L-Carnitine moiety assay: an up-to-date reappraisal covering the commonest methods for various applications.
L-Carnitine and its esters are typical endogenous substances. Their homeostatic equilibria are effectively controlled by various mechanisms which include rate-limiting enteral absorption, a multicomponent endogenous pool which is regulated according to a mammillary metabolism, an asymmetric body distribution and a saturable tubular reabsorption process leading to renal thresholds. In formal pharmacokinetic and metabolic investigations, the whole L-carnitine pool should be investigated, owing to the rapid interchange process between the various components of the pool. Free L-carnitine, as well as its acyl esters, must therefore be considered from an analytical viewpoint. L-Carnitine, acetyl-L-carnitine and total L-carnitine (the latter as an expression of the whole pool) can easily be assayed by enzyme or radioenzyme methods. Propionyl-L-carnitine and other esters containing fatty acids with more than three carbon atoms can be assayed using various HPLC approaches. Tandem mass spectrometry is another excellent approach to the assay of carnitine and its short-chain, medium-chain and long-chain esters. As L-carnitine contains a chiral carbon atom, the enantioselectivity of the assays is also considered in this review. Metabolites produced by enteral bacteria, namely tri-, di- and mono-methylamine, gamma-butyrobetaine, along with other systemic metabolites, namely trimethylamine N-oxide and N-nitroso dimethylamine, are very important in quantitative and toxicokinetic terms and require specific assay methods. This review covers the commonest methods of assaying carnitine and its esters, their impurities and pre-systemic and systemic metabolites and gives analytical details and information on their applications in pharmaceutics, biochemistry, pharmacokinetics and toxicokinetics.
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I.P.A.S. S.A., Clinical Pharmacology Department, Ligornetto, Switzerland.
Curti
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D002331:Carnitine / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D002675:Child, Preschool; D002849:Chromatography, Gas / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004952:Esters; D005260:Female; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*
D004952:Esters; D002331:Carnitine