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The first, sensitive, and rapid chiral method was developed for enatioseperations and determination of cabotegravir and its enantiomeric impurities by using HPLC and LC-MS. Cabotegravir is an antiretroviral medication used for the treatment of HIV/AIDS approved by the food and drugs administration (FDA) in the year 2021. The cabotegravir chiral separation was achieved on the coated cellulose-tris (4-chloro-3-methyl phenyl carbamate) (CHIRALCEL OX-3R) column in HILIC mode and the total run time is less than 15 min. The effects of mobile phase composition, elution mode, and percentage of organic modifier as well as the effect of mobile phase-additives and column temperature were investigated on selectivity, resolution, and peak symmetry. The mobile phase consisted of acetonitrile and water with 0.1% (v/v) addition of formic acid additive with the flow rate of 1 mLmin -1 . UV detection was carried out at 220 nm. The calibration curves of cabotegravir and its enantiomers were linear over the concentration range of 0.04-1.125 µgmL -1 . The limits of detection and quantification for cabotegravir and its enantiomer (RS isomer) were ≤ 0.02 and ≤ 0.06, and the RR and SS-isomers limits were ≤ 0.02 and 0.03 µgmL -1 respectively. It was demonstrated that the proposed method is selective, precise, and robust. Finally, the validated method was applied for the determination and identification of cabotegravir and its chiral enantiomers in the bulk drugs by using HPLC and LC-MS techniques., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

A selective, sensitive and robust chiral analytical method was developed for the quantification of Brivaracetam (BRV) and its three isomers. Systematic chiral chromatographic elution process was executed in different modes on chiral columns of polysaccharide based to attain the finest condition. The analytical method was developed by utilizing immobilized polysaccharide chiral column (CHIRALPAK IG-U) with reversed phase under isocratic condition containing acetonitrile and 10 mM ammonium bicarbonate in the proportion of 40:60 (v/v). The mobile phase flow rate and column temperature were monitored at 0.3 mLmin-1 and 25°C with a resolution of more than 2.0. The eluted components from the column were processed at 212 nm UV detection. The limit of detection and limit of quantification values of BRV, 2R, 4S-Isomer, 2R, 4R-Isomer and 2S, 4S-Isomers were found to be 0.0066/0.02, 0.0035/0.0107, 0.0036/0.0109 and 0.005/0.0152 µgml-1 respectively. Precision, linearity, accuracy and robustness were conducted according to ICH guidelines and the findings were within the acceptable limits. The proposed analytical method was found to be precise, accurate and specific for the quantification of enantiomer and its diastereomers for drug product and drug substance of BRV., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.

The enantioselectivity of proton pump inhibitors, namely, omeprazole, lansoprazole, rabeprazole, pantoprazole, tenatoprazole, and ilaprazole were studied using new generation chiral packing materials: CHIRALPAK IA, CHIRALPAK IB, and CHIRALPAK IC. Two versatile techniques, HPLC and supercritical fluid chromatography (SFC) were used in this study. CHIRALPAK IC has shown superior selectivity under both LC and SFC conditions, whereas CHIRALPAK IA has shown good selectivity in SFC when compared to LC under primary screening conditions. The chiral recognition ability in LC and SFC modes were found to be in the order CHIRALPAK IC > CHIRALPAK IA > CHIRALPAK IB. In addition to diode array detection, chiral detection was carried out using a laser polarimeter and the elution orders were found to be the same in both LC and SFC elution modes. Mobile phase modifiers and column temperature effects were also studied. In SFC, modifiers (cosolvent) elution strength was found to be in the order ethanol > methanol > 2-propanol > acetonitrile. In both LC and SFC, a decrease in retention and increase in resolution with an increase in temperature was noticed for all the proton pump inhibitors., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Novel thieno[2,3-d]pyrimidines containing a cyclohexane ring fused with a six- or five-membered heterocyclic moiety along with a benzylic nitrile were designed as potential inhibitors of PDE4. Expeditious synthesis of these compounds was carried out via a multi-step sequence consisting of a few key steps such as Gewald reaction, Dieckmann type cyclisation and Krapcho decarboxylation. This newly developed strategy involved construction of the thienopyrimidine ring followed by the cyclohexanone moiety and subsequently the fused heterocyclic ring. A number of thieno[2,3-d]pyrimidine based derivatives were synthesized using this method some of which showed promising PDE4B inhibitory properties. One of them was tested for PDE4D inhibition in vitro and dose dependent inhibition of TNF-α. A few selected molecules were docked into the PE4B protein the results of which showed good overall correlations to their observed PDE4B inhibitory properties in vitro. The crystal structure analysis of representative compounds along with hydrogen bonding patterns and molecular arrangement present within the molecule is described.