Distinguishing and determining method of entecavir chiral isomers

Abstract

The invention discloses a distinguishing and determining method of entecavir chiral isomers. The method comprises the steps of adopting a chiral ligand, metal ions and the eight entecavir chiral isomers to form complexes with different stable forms; utilizing a mass-spectrography method for recognizing and distinguishing the complexes, wherein the chiral ligand comprises R-besifloxacin, beta-cyclodextrin, migltol or cefotaxime; the metal ions comprise alkaline-earth metals or transient state metals; the alkaline-earth metals comprise Mg and Ca; the transient state metals comprise Ni, Cu, Co, Zn and Mn. The method is fast, simple and convenient, overcomes the defects that a traditional HPLC method needs a specific chiral stationary phase, solvent gradient eluting consumed time is longer, and an enantiomeric separation degree is insufficient, and can be used for quickly distinguishing the eight entecavir chiral isomers and quantitatively determining.

Description

Technical field [0001] The invention belongs to the technical field of mass spectrometry, and is used for distinguishing chiral isomers of medicines, in particular to a mass spectrometry kinetic method for separating entecavir chiral isomers. Background technique [0002] Entecavir (entecavir, ETV) is a cyclopentylguanosine nucleoside analogue. At present, this drug is the first-line drug for the antiviral treatment of chronic hepatitis B. There are 3 chiral centers in its structure, which can produce 8 optical anomalies. Conform, clinical medication is a single isomer (1S, 3R, 4S). (1S, 3R, 4S); (1R, 3S, 4R); (1S, 3S, 4R); (1R, 3R, 4S); (1S, 3R, 4R); (1R, 3S, 4S); ( 1R, 3R, 4R); (1S, 3S, 4S) These 8 configurations correspond to the numbers ETV1; ETV2; ETV3; ETV4; ETV5; ETV6; ETV7; ETV8. The structural formula of ETV1 is as follows: [0003] [0004] According to the relevant provisions of the guidelines for the analysis of drug impurities in the 2015 Chinese Pharmacopoeia, in a...

AI Technical Summary

Problems solved by technology

At present, the existing methods for separating entecavir chiral isomers are mainly high-performance liquid chromatography. These methods require specific chiral stationary phases, and the solvent gradient elution takes a long time, and cannot realize the eight chiral isomers of entecavir. The separation of enantiomers, especially the insufficient separation of enantiomers, the analysis of drugs with multi-chiral centers is a difficult point for the separation of chiral impurities

After searching the literature, there is no report on the method that can simultaneously separate the eight chiral isomers of entecavir

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