Factors Controlling Precision and Accuracy in Isotope-Ratio-Monitoring Mass Spectrometry

Abstract

The performance of systems in which picomole quantities of sample are mixed with a carrier gas and passed through an isotope-ratio mass spectrometer system was examined experimentally and theoretically. Two different mass spectrometers were used, both having electron-impact ion sources and Faraday cup collector systems. One had an accelerating potential of 10kV and accepted 0.2 mL of He/min, producing, under those conditions, a maximum efficiency of 1 CO2 molecular ion collected per 700 molecules introduced. Comparable figures for the second instrument were 3 kV, 0.5 mL of He/min, and 14000 molecules/ion. Signal pathways were adjusted so that response times were <200 ms. Sample-related ion currents appeared as peaks with widths of 3-30 s. Isotope ratios were determined by comparison to signals produced by standard gases. In spite of rapid variations in signals, observed levels of performance were within a factor of 2 of shot-noise limits. For the 10-kV instrument, sample requirements for standard deviations of 0.1 and 0.5% were 45 and 1.7 pmol, respectively. Comparable requirements for the 3-kV instrument were 900 and 36 pmol. Drifts in instrumental characteristics were adequately neutralized when standards were observed at 20-min intervals. For the 10-kV instrument, computed isotopic compositions were independent of sample size and signal strength over the ranges examined. Nonlinearities of <0.04%/V were observed for the 3-kV system. Procedures for observation and subtraction of background ion currents were examined experimentally and theoretically. For sample/ background ratios varying from >10 to 0.3, precision is expected and observed to decrease approximately 2-fold and to depend only weakly on the precision with which background ion currents have been measured.

Recent developments in the use of isotope ratio mass spectrometry in sports drug testing

“…The difference between the mean values was found to be highly significant with p<0.001 (t test) Factors influencing GC/C/IRMS determinations Since its invention, GC/C/IRMS has been investigated to prevent possible sources of problems, which may invalidate the isotope ratio determinations [24,111]. In 1994, the first review on "Factors controlling precision and accuracy…" was published, dealing with problems of non-linearity, necessary sample sizes and instrument drift over time [112]. At the same time, an investigation on possible isotopic fractionation during HPLC fractionation was published [113].…”

Isotope‐ratio detection for gas chromatography

“…Due to the discrete nature and stochastic distribution of ions, the precision with which we would estimate the average ion current increases as the square root of the number of ions counted, a property governed by the Poisson distribution and familiar to all scientists that rely on counting finite numbers of randomly distributed particles. The attainable precision for isotope-ratio measurements is thus fundamentally limited by the number of ions of the rare isotope that are counted, known as the "shot-noise" limit [33]. This limitation combines both the ionization efficiency of the mass spectrometer and the relative abundance of the rare isotope.…”

“…For carbon, modern methods and instrumentation have reduced noise sources to such a level that isotopic measurements commonly achieve precision that is within a factor of 10 of that imposed by the shot-noise limit [33]. For other elements, increased noise sources and systematic bias due to analyte handling and conversion lead to worse precision, such that achievable precision is commonly a factor of 100 or more above that of the shotnoise limit [34].…”

“…To obtain the highest possible accuracy, isotope-ratio analyses require comparison of sample and standard within each chromatogram [33]. The goals for this standardization are two-fold.…”

“…In an ideal chromatogram, a single standard would be sufficient to calibrate all analyte peaks. In reality, d values become less accurate as sample/standard pairs are more widely separated due to the effects of instrument drift [33]. To compensate for drift, most software interpolates linearly between the two closest standards to calculate the isotope ratio of a (hypothetical) standard eluting at the same retention time as the analyte.…”