Analysis of stereoisomers of chiral drug by mass spectrometry

Abstract

Chiral molecules are of great importance in the life science since individual enantiomers may differ in biological activity, mechanism, and toxicity, making it necessary to explore efficient chiral analysis methods. Chromatography approaches are often used to differentiate enantiomers while mass spectrometry (MS) was thought to be blind in chiral analysis. With the development of MS technique, it began to play a more and more crucial part in chiral observation. In this review, we will give a detailed introduction of the analysis methods related to MS for chiral drugs, including its mechanism, applications, and future development.

Acid‐based approach for separation of peptide epimers using IM‐MS

“…Apart from the technical issues of using P1-d 5 , helpful in examination of the influence of the mobility parameters such as wave velocity, wave height, nitrogen, and helium pressure, the use of P1-d 5 allowed the thorough examination of specificity issues of complex formation, which could lead to the false negative results in terms of epimer separation in the case of the analysis of the mixture of epimers. The overlapping of ion mobility peaks of P1 and P1-d 5 was verified for each of the analyzed complexes (an example is shown inFigure S2, Supporting Information).Table 1summarizes the results of the acidic complexation on mobility separation between P1-d5 and P2 epimers-the drift time differences between acidic complexes of P1-d 5 and P2. The data are reported for deprotonated peptide-acid complex ions, for peptide to acid ratio 1:1 and 1:2 where applicable, and sodiated complexes in positive ion mode for a few examples for which the increase of epimer separation was observed.…”

“…Two approaches are commonly used: indirect approaches, based on other techniques used in tandem with mass spectrometry (eg, chromatographic or capillary electrophoretic techniques) and the direct approach, which takes advantage of the differences in physicochemical gas‐phase properties of diastereoisomeric ions. Consequently, diastereoisomeric ions or newly formed ionic complexes with a chiral selector may be separated based on their distinguishing fragmentation pathways, intensities of ionic fragments, or decomposition energetics . A recently issued review summarized the strategies for analysis of isomeric peptides …”

“…Consequently, diastereoisomeric ions or newly formed ionic complexes with a chiral selector may be separated based on their distinguishing fragmentation pathways, intensities of ionic fragments, or decomposition energetics. [4][5][6][7][8] A recently issued review summarized the strategies for analysis of isomeric peptides. 9 Ion mobility mass spectrometry (IM-MS) presents a different concept of stereoisomer discrimination.…”

Direct differentiation of stereoisomers of ezetimibe/ambrisentan/atorvastatin and their mechanism study by electrospray ionization quadrupole time‐of‐flight mass spectrometry

“…Chirality is essential in life processes, and most of the bioactive compounds of living organisms are chiral molecules . In the pharmaceutical field, the enantiomers of a chiral drug show striking differences in terms of biological activity, potency, and toxicity; enantiomeric pure products are therefore desirable ones in drug candidates . For this reason, the US Food and Drug Administration (FDA) guidelines recommended the study of enantioselective identity and stability for the contributions of individual enantiomers to pharmacological and toxicological activity…”

“…1 In the pharmaceutical field, the enantiomers of a chiral drug show striking differences in terms of biological activity, potency, and toxicity; enantiomeric pure products are therefore desirable ones in drug candidates. 2,3 For this reason, the US Food and Drug Administration (FDA) guidelines recommended the study of enantioselective identity and stability for the contributions of individual enantiomers to pharmacological and toxicological activity. 1 Various of methods has been used for the separation of enantiomers, such as high-performance liquid chromatography (HPLC), gas chromatography (GC), supercritical fluid chromatography (SFC), thinlayer chromatography (TLC), and capillary electrophoresis (CE).…”