Other analytical techniques

Lithium has been used in the treatment of manic-depressive disorder since 1970, and the narrow therapeutic index of lithium with the nonspecific nature of lithium toxicity prompted routine therapeutic monitoring for these patients. Methodologies available for routine determination of lithium in human serum or plasma include flame atomic emission spectroscopy, flame atomic absorption spectroscopy, potentiometry with lithium ion-selective electrodes, and colorimetric methods with spectrophoto-metric determination of lithium concentration and reflectometry methods. Sampson et al. evaluated determination of lithium by five ion-selective electrodes and one colorimetric method by comparing the results obtained by flame atomic absorption and flame atomic emission spectroscopy. The colorimetric method was based on the shifting of absorbance of a crown ether chromophore when it binds lithium (Vitros; formerly Ektachem slide) (63). For colorimetric determination of lithium, aromatic organic reagents such as crown ethers and amide ionophores are used. Crown ether and cryptands provide best selectivity for lithium. The cryptand phenol exhibits greater than 4000:1 selectivity for lithium compared with sodium for binding because of rigid configuration of a binding site for lithium to form the complex. This complex is also water-soluble. Crown ether with bulky groups inhibits formation of 2:1; crown : sodium complex while allowing 1:1; crown : lithium complex (64).

The frequent use of platinum complexes in cancer therapy may require therapeutic monitoring of platinum in serum. Using 400 ^L specimen, Kloft et al. described a rapid flameless atomic absorption spectrometric assay of platinum in serum or in the protein free ultrafiltrate (free platinum). The limit was detection for platinum was 40 ng/mL in serum and 20 ng/mL in ultrafiltrate (65).

Supercritical fluid and microbore liquid chromatography may have potential application for drug analysis. In supercritical fluid chromatography (SFC), the mobile phase is a gas (for example, carbon dioxide) maintained at its supercritical state. This mobile phase has low viscosity of a gas and high diffusivity between that of a gas and liquid. SFC analysis can be performed with a GC or LC detector and mass spectrometry can certainly be used as a detector for SFC. Potential applications include analysis of a small amount of specimen (5-200 ^L) for pediatric and neonatal TDM as well as drug confirmation for toxicology (66). Graves et al. (67) used SFC for characterization of a labile digitalis-like factor.

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