Isotope Dilution Mass Spectrometry (IDMS)

What is Isotope Dilution Mass Spectrometry (IDMS)?

Isotope dilution mass spectrometry is a method in which stable isotope-labeled compounds of known mass and abundance are added to a sample as a diluent, mixed homogeneously, and then the change in isotope abundance before and after mixing is determined by mass spectrometry, and finally the elemental content of the sample can be calculated. Isotope dilution analysis is a method used to determine the amount of a chemical substance and is categorized as an internal standard method. This is because the standard substance (in the form of the analyte's isotopic enrichment) is added directly to the sample. Unlike conventional analytical methods, it relies not only on signal intensity, but also uses signal ratios. The isotope dilution method is considered to be one of the most metrologically accurate of the chemical measurement measures. Isotope dilution methods are divided into stable isotope dilution and radioisotope dilution.

• Stable isotope dilution uses a mass spectrometer to measure changes in mass, while radioisotope dilution measures changes in the radioactivity ratio (the intensity of radioactivity per unit weight of material) by means of a counter.
• Stable isotope dilution is expensive and takes longer to measure, but it is able to measure less dilution and is less sensitive. In contrast, the radioisotope dilution method is simple and easy to perform, and its sensitivity is comparable to that of activation analysis, so it is more widely used in practical applications and has gained more scope for development.

Advantages of Isotope Dilution Mass Spectrometry

• High Sensitivity: The method enables detection of very low concentrations of target substances, giving it excellent sensitivity at the trace level.
• High Accuracy: Using the ratio of isotopically labeled substances for quantitative analysis effectively reduces sources of error and improves the accuracy of measurement results.
• High Selectivity: Isotope labeling provides a unique mass spectral signal, making the detection of target substances in complex matrices more reliable and reducing the influence of interfering substances.
• Wide Applicability: Applicable to a wide range of sample types, including biological samples, environmental samples, etc., and can be used to determine a wide range of elements and compounds.
• Tracking the Dynamic Changes of Substances: It can be used to study the metabolism and migration of substances in organisms or in the environment, revealing the dynamic behavior of substances.
• Low Detection Limit: Due to the introduction of isotope labeling, it is possible to achieve efficient detection of low concentrations of target substances, reducing the detection limit.
• Wide Quantitative Range: It can cover the measurement of target substances from traces to high concentrations, and has a wide range of applications.

Requirements for Isotope Dilution Mass Spectrometry

The principle of Isotope Dilution Mass Spectrometry (IDMS) is based on the fact that many elements have two or more stable isotopes in nature and their ratios remain constant. In IDMS, a certain amount of one stable isotope is added to the sample and the ratio between the isotopes is then measured by a mass spectrometer.

• The target analyzed element must have multiple isotopes.
• The isotopes must be measured without interference from homogeneous isomers, which requires the use of a high-resolution mass spectrometer.
• The sample and additions of stable isotopes must be in isotopic equilibrium.
• Isotope dilution analysis can correct problems such as interference, analyte loss and instrument drift that occur after the addition of stable isotopes. Two different modes can be distinguished when performing morphological analysis, including specific isotope dilution (this method is used to measure an element in a specific form, and it helps to accurately determine the concentration of that specific form) and non-specific isotope dilution (in this method, the specific form of the element is not of interest, but rather the total amount of the element. It provides information about the overall concentration of the element in the sample).

Calculation of Radioactivity Ratio in IDMS

The basic principle of IDMS is to mix and exchange the stable isotope (assay or carrier) and the radioactive isotope (indicator or assay). After dilution of the isotopes, a portion of the measured element is separated, and the chemical separation yield and radioactivity are determined (to find the radioactivity ratio).

Direct Dilution Method

• A1 is the total radioactivity introduced by the indicator and A2 is the separated radioactivity (A2
• w1 is the weight of the measured element introduced by the indicator.
• wk is the weight of the measured element (non-radioactive) originally contained in the specimen.
• w2 is the weight of the measured element isolated (w2
• s2 is the diluted radioactivity ratio, and s2 is also the radioactivity ratio of the separated part (w2).

The formula for calculating wk is as follows:

Inverse Dilution Method

The substance to be measured is radioactive and is diluted by adding a non-radioactive carrier. This method is often used in nuclear chemistry, fission product analysis, and activation analysis.

• A0 is the radioactivity to be measured.
• w1 is the amount of carrier added.
• w2 is the amount of carrier separated (w2
• A2 is the radioactivity of the separated portion (w2).

Trace amounts of labeled compounds are often used in biochemical studies where their content needs to be determined (e.g. to study the distribution after metabolic action. The radioactivity ratio of the measured marker in this case is known. 

• wk is the amount of the measured substance with a radioactivity ratio of s1=A0/wk.
• w1 is the amount of carrier added.
• s2=A0/(wk +w1) is the radioactivity ratio after dilution (which can be measured from the fractionated portion).

Double Dilution Method

This method is commonly used in biochemical studies where the measured material is radioactive and its radioactivity ratio is unknown.

• s1 is the original radioactivity of the test material.
• s2 is the radioactivity after the first dilution.
• w1 (mg) is the amount of the first carrier addition.

Applications of Isotope Dilution Mass Spectrometry

• Trace Element Determination: Isotope Dilution Mass Spectrometry (IDMS) can be used to determine the concentration of trace elements, such as iron, zinc and copper, in biological samples. This is of great significance for the study of human health, the metabolism of elements in living organisms and the pathogenesis of related diseases.
• Drug Metabolism Research: Isotope-labeled drugs and drug metabolites can be used to study the metabolic pathways, metabolite production rates, and drug clearance processes in the body using isotope dilution mass spectrometry (IDMS). This is a guide for drug development and optimization of clinical use.
• Hormone Measurement: Used to determine the level of hormones in organisms, such as thyroid hormone, growth hormone, etc.. This is important for understanding the physiological role of hormones, the study of the function of the endocrine system and the diagnosis of hormone-related diseases.
• Protein Metabolism: Isotope Dilution Mass Spectrometry can be used to study protein synthesis, degradation, and steady-state levels. By labeling amino acids or other protein components, it can track dynamic changes in proteins, which can help to reveal the mechanisms of protein metabolism in organisms.
• Radioisotope Therapy Monitoring: In the development of nuclear medicine therapies, isotope dilution mass spectrometry can be used to monitor the distribution, metabolism, and elimination of radioisotopes in the body in order to monitor the efficacy and safety of the therapy.
• Environmental Science: Isotope dilution mass spectrometry is used to track and monitor the source and distribution of pollutants, to study elemental levels in groundwater and soil, and elemental cycling in the atmosphere.