The goal of the present research has been to develop a selective analytical detection procedure for the easy identification and assay of drugs and related substances present in complex mixtures, without a chromatographic separation step or other work up. The detector of choice is circular dichroism (CD) spectropolarimetry which has the appropriate balance between degree of analytical selectivity and breadth of application. Applications that are described are selected from work carried out in the context of forensic, clinical, and pharmaceutical chemistries, and specifically include discussions of the analyses of enantiomeric mixtures of nicotine and cocaine, the D and E vitamins, and cholesterol and other steroids.

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Data on total cholesterol (TC) and its distribution among the three solubilizing lipid fractions in human serum have been obtained from three independent laboratories, and binary linear correlations between TC and each of the various fractions are compared. Two sources used the approved double-enzymatic multistep Allain-Trinder reaction with absorption detection. In the third method, which is entirely new, a nonenzymatic chromogenic reaction and circular dichroism (CD) detection were used. TC results from all three sources are in excellent agreement. HDL-C values measured by both enzymatic methods also agree in their correlations with TC but these are quite different from the correlation observed between HDL-C and TC values obtained by the new nonenzymatic procedure. Reasons are given which suggest that the nonenzymatic method is more accurate for the measurement of the low-density lipid fractions and why health risk determinations that are based upon calculated values for this variable should be deemphasized until a more dependable procedure is approved for use.

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