Application of an unusual ninhydrin-based reaction for the indirect chiral resolution of d,l-penicillamine

An unusual reaction involving ninhydrin and aminothiols was exploited to set an indirect method for the chiral recognition of stereoisomers of penicillamine. Separation of diastereoisomers was achieved on a C18 column in isocratic mode by using a mixture of propionic acid (pH 3.0)/acetonitrile/water (10:10:80, v/v/v) as a mobile phase. Diastereoisomers were detected by a fluorescence detector in fairly short times (about 7 min) and with a good resolution. The lowest detectable amount of toxic isomer of penicillamine (l-enantiomer) in samples of the d-enantiomer, was around 0.01%. The method was also suitable for the indirect chiral recognition of other aminothiols such as cysteine and cysteinylglycine.