Direct Separation of Pregabalin Enantiomers Using a Zwitterionic Chiral Selector by High Performance Liquid Chromatography Coupled to Mass Spectrometry and Ultraviolet Detection

Abstract

Abstract:The chromatographic resolution of pregabalin enantiomers has been often achieved by derivatization of the molecule, in order to reach enough sensitivity at low concentrations of the minor enantiomer present in the active principle. In the present article, the development and optimization of two liquid chromatographic methods are presented for the direct resolution of pregabalin enantiomers on a chiral stationary phase (CSP) containing a zwitterionic selector derived from cinchona alkaloid and sulfonic acid (CHIRALPAK ZWIX). The key parameters for the separation as well as the compatibility of chromatographic conditions with different detection modes (ultraviolet and mass spectrometry) were investigated. The resulting methods were found to be selective, of high performance and low limits of detection (2 µg/mL by UV and 1 ng/mL by MS, respectively) and quantification (6 µg/mL by UV and 5 ng/mL by MS, respectively) for the minor enantiomer which is considered as a chiral impurity.

Preparation and evaluation of a deoxycholic‐calix[4]arene hybrid‐type receptor as a chiral stationary phase for HPLC

“…The two dl ‐amino acids ( dl ‐leucine and dl ‐valine) were derivatized with 3,5‐dinitrophenyl to increase the π‐acidity. Pregabalin and omeprazole are both among drugs in which only their S isomer is active . The R form of mandelic acid acts as a key intermediate in the production of semisynthetic penicillins and cephalosporins, and diclofop‐methyl is an organochlorine herbicide for which its R enantiomer shows significantly greater herbicidal activity .…”

Construction and verification of CYP3A5 gene polymorphisms using a Saccharomyces cerevisiae expression system to predict drug metabolism

“…Genotypes for the CYP3A5 polymorphisms were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism as previously described (13). Blood drug concentrations of each CYP3A5 genotype group was measured with liquid chromatography-mass spectrometry (LC-MS) (14,15) and high performance liquid chromatography (HPLC) (16). The metabolic rate of amlodipine was calculated in each group.…”

Interpol review of controlled substances 2016–2019

“…Pregabalin: 2016 Direct Separation of Pregabalin enantiomers using a Zwitterionic chiral selector and analysis by two HPLC methods including detection by MS and UV [ 394 ]; results of a national study of Pregabalin abuse in France [ 395 ]; preparation and evaluation of floating tablets of pregabalin prepared in differing concentrations of xanthan and guar gum [ 396 ]; review article on the use of separation techniques including HP-TLC, HPLC, GC and electrophoresis in the determination of antiepileptic drugs including pregabalin (also includes eslicarbazepine acetate, levetiracetam, lacosamide, oxcarbazepine, and retigabine) [ 397 ]; study of the abuse potential of pregabalin [ 398 , 399 ]; validated fluorometric UHPLC method to measure pregabalin [ 400 ]; Thermomyces lanuginosus lipase for the efficient production of (S)-2-carboxyethyl-3-cyano-5-methylhexaoic acid used as chiral intermediate for pregabalin [ 401 ]; 2017 gabapentin diversion and misuse from 2002-2015 based on law enforcement-derived data [ 402 ]; abuse and misuse of Pregabalin and Gabapentin [ 403 ]; Pregabalin misuse and abuse reported to US Poison Centers [ 404 ]; synthesis of (+/−)-Pregabalin by using a three-step sequential-flow system with heterogeneous catalysts [ 405 ]; survey of the use of pregabalin among users of illicit drugs in Southern Germany [ 406 ]; systematic review of the effectiveness of policies restricting access to pregabalin [ 407 ]; Pregabalin abuse in Munich [ 408 , 409 ]; 2018 literature review of the abuse potential of pregabalin [ 410 ]; formulation of controlled-release tablets containing 150 mg pregabalin [ 411 ]; pregabalin immediate release tablets were prepared by direct compression method using central composite design with response surface methodology [ 412 ]; Preparation and evaluation of non-effervescent tablets containing pregabalin [ 413 ]; synthesis method of racemic Pregabalin, Baclofen and 3-Phenibut involving Lossen rearrangement [ 414 ]; Pregabalin misuse in methadone maintenance treatment patients in Israel [ 415 ]; 2019 validated GC/MS for the evaluation and quantification of pregabalin in pharmaceutical preparations [ 416 ];…”