Mass spectrometric assay of stable isotopic enrichment for the estimation of protein turnover in man

The isotope ratio mass spectrometer Dual inlet double collector gas isotope ratio mass spectrometers by inherent design, possess a low resolving power but extremely high sensitivity. These specialized instruments are capable of precise estimates of the heavy isotopic content of pure, low molecular weight permanent gases such as H,, CO,, N, and SO,. For present purposes, consideration will be given only to the heavy nonradioactive isotopes of carbon and nitrogen. The low resolution is due primarily to the very short analyser tube (and thus the ion beam path length), the width of the final resolving slits and the low strength of the permanent magnet. The high sensitivity is achieved by directly comparing the isotope ratio of the sample gas to that of a reference gas. The complete gas inlet system, situated in front of the analyser tube, is characteristically composed of variable volume bellows (reservoirs), metal capillaries and an automatic all metal changeover valve. The bellows permit equalization of pressures with respect to sample and reference gas as the ratio ultimately obtained is pressure dependant; the capillaries, crimped at their distal end, convert viscous to molecular gas flow such that the isotopic content of the gas entering the analyser is identical to that in the reservoirs. Finally, the changeover valve serves two purposes; it permits alternate entry of sample and reference gas into the analyser on a strict time basis and simultaneously permits the gas not entering the analyser to be bled away at an equal rate, thus maintaining the status quo with respect to pressure between the reference and sample gases. The mass spectrometer itself consists of the analyser (flight tube) that houses an ion source, ion collectors and a deflection region (shown in Fig. I). If one takes nitrogen gas as an example, the objective of isotopic analysis is to separate the m/e 28 (major) and 29 (minor) ion species (N retains its diatomic molecular structure) such that they can be collected and measured separately and a ratio of their intensities obtained. On entering the ion source gas molecules are ionized in a stream of electrons, extracted from the source under the influence of an accelerating voltage as a mixed ion beam, which is segregated on passage through the magnetic field into component ion beams of fixed mass:charge value. The