A mass spectrometric method is introduced for rapid and accurate chiral quantification by examining a trimeric metal complex into which a chiral reference is incorporated with the analyte. Several metal ions (CuII , NiII , MgII , MnII , CoII , and ZnII ) were selected as the central metal ion, and chiral drugs ezetimibe (EZM) and ambrisentan (AMB) were used as the reference to each other for isomeric differentiation by using electrospray ionization quadrupole time-of-flight mass spectrometry. Doubly charged trimeric cluster ions instead of the singly charged clusters were applied in this study. Kinetic method (KM) and chiral recognition (CR) method were used for construction of a calibration curve for chiral quantitation. The results from the two methods were found to be complementary to each other, which improved quantitative analysis of stereoisomers for EZM. Furthermore, we have successfully used S-AMB as reference for the chiral differentiation of enantiomeric atorvastatin (ATO), which is frequently combined with EZM as a codrug. Experimental results showed that the binary mixture of EZM and ATO enantiomers can be determined simultaneously without prior separation steps. The direct measurement of chiral purity within 5% was demonstrated. This mass spectrometric method represents an effective alternative to commonly used chromatographic techniques as means of chiral purity determination and is of potential use in rapid screening experiments.
Keywords: ESI-QToF mass spectrometry; ambrisentan; atorvastatin; enantiomeric and diastereoisomeric differentiation and quantification; ezetimibe.
© 2018 John Wiley & Sons, Ltd.