Stable isotope labelled compounds as internal standards

STABLE ISOTOPE LABELLED COMPOUNDS AS INTERNAL STANDARDS 

The purpose of an internal standard in analytical techniques is to correct for losses of a compound under study. There must therefore be both chemical similarity and similarity of behaviour between the standard and the compound subject to examination. When gas chromatography-mass spectrometry is employed in drug metabolism studies, mass differences alone can be used to discriminate between the compound analysed and the standard. Thus an isotopically labelled compound represents the ideal standard. This forms the basis of a most important application of stable isotopes in drug research. 

The use of deuterated nortriptyline and deuterated-[ N]nortriptyline was investigated for the estimation of nortriptyline in plasma [158]. The labelled standard was added to the crude sample before gas chromatography-mass spectrometry. In other drug applications, the labelled drug has been added prior to extraction, derivatisation, and analysis [145]. 

Analytical procedures have been developed utilising chemical ionisation mass spectrometry in conjunction with stable isotope labelled amines to obtain quantitative information on the metabolism of (/ -), (.S-), and (R.S-) methyldopa (alpha-methyldopa) and the regional concentrations of dopamine, a-methyl-dopamine, noradrenaline (norepinephrine) and a-methyinoradrenaline in rat brain. C-labelled (5)-a-methyldopa, as well as deuterated amines, were employed. Isotope dilution techniques provided good quantitative data [164]. 

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The use of stable isotope labeled compounds as internal standards requires MS detection... 

Quantitative Applications - The use of stable-isotope-labeled compounds as internal standards for the quantitation of drugs and metabolites in biological fluids offers a unique combination of sensitivity and selectivity of detection for pharmacokinetic studies. The principles of the technique have been outlined, and applications up to 1981 have been compiled. Specific aspects of the isotope dilution method, e.g. its utility as a reference technique and associated procedures for handling the data generated from the use of multiple isotope tracers simultaneously, have been discussed. Examples of isotope dilution methods used in clinical psychopharmacology have also been reviewed. ... 

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