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Isotope Dilution in Chemical Analysis


The technique of isotope dilution is being used more and more in our lab to improve precision and accuracy by reducing the problems with calibration and sample preparation matrix effects.  Some analytes 

are not well behaved during chromatography or sample extraction. Variability caused by such problems is usually compensated for in part or monitored by using internal standards and surrogate analytes.  An isotope dilution standard is the "perfect" internal standard or surrogate. 

Isotope Dilution Analysis using ICPMS

Isotope Dilution Standards

An internal standard or surrogate is a compound similar to the analyte of interest.  An isotope dilution standard is an isotope of an element or a molecular compound labeled with an isotope.  Good examples of both of these are 204Pb and benzene-d6.   204Pb is a minor isotope of lead (Pb).  The Pb isotopes which are stable and occur naturally have atomic masses of 204 (1.4%), 206 (24.1%), 207 (22.1%), and 208 (52.4%) where the natural abundances  appear in parenthesis.  By adding a known amount of 204Pb to a sample before testing for total Pb and by testing for each of the lead isotopes, one can accurately determine how much total 

Pb was in the sample.   There are a couple of catches, because nothing is ever "perfect".   One catch is that you need to use a mass spectrometer to separate analyte masses.   A second catch is that enriched isotopic standards are expensive. The other catches are beyond the scope of this article.

In the example benzene-d6, the hydrogens (H) normally attached to the benzene ring are replaced by deuteriums (D), an isotope of  hydrogen (2H), thus the -d6.  In both these cases, the isotopes have almost exactly the same chemical properties as the original or naturally occurring isotopes.  They just differ in mass.  This is as close as it gets to a "perfect" internal standard or surrogate.

Isotope Dilution Analysis by GCMS

Minimizing Errors

To give you an idea of how much the error can be reduced in a chemical analysis, consider the following.  In a gas chromatography analysis, the error from injection can be approximately 5%.  By adding an internal standard, the error can be reduced by half to approximately 2-3%.  With isotope dilution, the error should be half of that again, approximately 1%.  In the analysis of sub-ppm levels of lead (Pb) in supplements, errors from traditional approaches using ICPMS and GFAA can be 25% or more, characteristic of a trace analysis in a solid matrix.  With isotope dilution, the error is generally less than 5%.  Where ever a mass spectrographic technique can be used for analysis, isotope dilution should minimize the error.  

Because of this, NIST commonly uses isotope dilution mass spectrometry for certifying reference samples.

Below are links to other articles on isotope dilution techniques using either gas chromatography-mass spectrometry (GCMS) or inductively coupled plasma-mass spectrometry (ICPMS).

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