Applications to analytic chemistry: an evaluation of stable isotopes in mass spectral drug assays.

We evaluated stable isotope analogues (SIAs) as internal standards in mass spectral drug assays on the analytic parameters of accuracy, precision, specificity, and limit of quantitation. Only one literature report suggests that the use of an SIA made an assay more accurate, although theoretic considerations strongly support their use. There is substantial evidence, however, that their use made assays more precise. Potentially, the chromatographic peak shape and retention time of the SIA can be compared with those of the analyte to support assay specificity, and this type of comparison has been implemented as a new computer program (QSIMPS). There is some evidence that SIAs can serve in "carrier" substances to increase recoveries and thus lower the limit of quantitation of an assay. However, the use of large amounts of an SIA (relative to the analyte) leads to analytic imprecision, because of memory effects, large blank values, and unacceptable confidence limits.