Nickel(II)‐assisted enantiomeric differentiation and quantitation of tadalafil by direct electrospray ionization mass spectrometry

Abstract

A facile method based on electrospray mass spectrometry was established and validated for the differentiation of enantiomeric tadalafil isomers without using chiral chromatographic separation. The enantiomers were coupled with a chiral selector to form diastereomeric complex ions. Nickel-tadalafil complexes, [Ni (tadalafil)(l-Trp)-H] , produced a characteristic fragment ion at m/z 524 by loss of 1-methyl-1,6-dihydropyrazine-2,5-dione via collision-induced dissociation. The relative abundance of this fragment ion to the precursor contributed to differentiate tadalafil enantiomers, and energy-resolved product-ion spectra were applied to determine the molar composition of tadalafil in the mixture (R,R and S,S) as well. In addition, the other two forms of stereomeric isomers of tadalafil (R,S and S,R) could be also distinguished and analyzed by this method. The method was validated in different types of mass spectrometers (AB quadrupole time-of-flight and Bruker ion trap) and also verified by a chiral high-performance liquid chromatography coupled with quadrupole time-of-flight. The chiral determination of tadalafil using MS method proved to be rapid (1-min run time for each sample) and to have the same accuracy and precision comparable to chiral liquid chromatography mass spectrometry methods. This method provides an alternative to commonly used chromatographic technique for chiral determination and is particularly useful in rapid screening in enantioselective synthesis and enantiomeric impurity detection in pharmaceutical industry. Copyright © 2017 John Wiley & Sons, Ltd.

Chiral detection of entecavir stereoisomeric impurities through coordination with R‐besivance and ZnII using mass spectrometry

“…More research is needed to improve the sensitivity of this method and contribute to its utility in enantioselectivity research of biological samples in vivo . In summary, this study and previous research results suggest that the KM may have great applications in the near future in the practical analysis of chiral drugs.…”

Analysis of stereoisomers of chiral drug by mass spectrometry

“…. 38,39 Besides, the same group also applied this method in the differentiation of entecavir by forming complex with R-besivance and Zn II . 37 Wang infused the sample [Ni II (tadalafil)(L-Trp)-H] + directly to the MS to perform the enantiomeric differentiation and quantitation of tadalafil.…”

“…Therefore, it is of great significance and practical value to develop a highly selective, simple, fast, and stable chiral analysis method using MS for the existing and potentially large chiral drugs present on the market. 38,39,[64][65][66][67] Amino acids, glucose isomer, DMEB*, polylactide, and catechin epimers Ion mobility mass spectrometry: small chiral molecules were successfully distinguished by calculating the molecular collision cross section. Amino acids, amino acid esters, and amino alcohols Ion/molecule reactions: host compounds can be tetra-amide macrocycles or resorcinarene.…”

Chiroptical and vibrational spectroscopic study of genuine and counterfeit medicines containing tadalafil

“…High-performance liquid chromatography, usually in tandem with mass spectrometry, is often considered to be the most important and commonly used method in pharmaceutical analysis, and the issue of PDE-5 inhibitors is not an exception. 30 In this study, VCD and ECD were used for the spectroscopic analysis of genuine and counterfeit Cialis® 20 mg tablets. 5,[8][9][10] Counterfeit medicines containing tadalafil were also studied by nuclear magnetic resonance (NMR), 11 Raman, 11 and infrared (IR) spectroscopies 7,12,13 or X-ray fluorescence.…”