Development of HPLC-CAD method for simultaneous quantification of nine related substances in ursodeoxycholic acid and identification of two unknown impurities by HPLC-Q-TOF-MS.

Ursodeoxycholic acid has gained increasing attention due to its recent discovery of the preventive effect on SARS-CoV-2 infection. Ursodeoxycholic acid has been included in various pharmacopoeias as an old drug, and the latest European Pharmacopoeia lists nine potential related substances (impurities A∼I). However, existing methods in pharmacopoeias and literature can only quantify up to five of these impurities simultaneously, and the sensitivity is inadequate, as the impurities are isomers or cholic acid analogues lacking chromophores. Herein, a novel gradient RP-HPLC method coupled to charged aerosol detection (CAD) was developed and validated for the simultaneous separation and quantification of the nine impurities in ursodeoxycholic acid. The method proved sensitive and allowed the quantification of the impurities as low as 0.02 %. Relative correction factors of the nine impurities were all within the range of 0.8-1.2 in the gradient mode by optimizing chromatographic conditions and CAD parameters. In addition, this RP-HPLC method is fully compatible with LC-MS due to the volatile additives and high percentage of the organic phase, which can be directly used for the identification of impurities. The newly developed HPLC-CAD method was successfully applied to commercial bulk drug samples, and two unknown impurities were identified by HPLC-Q-TOF-MS. The effect of CAD parameters on the linearity and correction factors was also discussed in this study. Overall, the established HPLC-CAD method can improve the methods in current pharmacopoeias and literature and contributes to understanding the impurity profile for process improvement.

Networked frame contestation from authoritarian to Western democracy – A case of China's (failed) Twiplomacy in contesting coronavirus narrative in the UK

Transnational political communication today is being reconfigured by digital technologies and global power transition. Authoritarian state actors such as China are increasingly active on global social media platforms such as Twitter to directly advance their preferred frames with foreign publics in Western democracies, most notably in what could be called Chinese Twiplomacy contesting narrative globally over contentious issues. This paper problematises such Twiplomacy from authoritarians to Western democracies as ‘networked transnational frame contestation', arguing that the political and cultural distance between the sending and target countries, the networked affordance of social media, and the national prism of the target countries, all contribute importantly to the complexity of such frame contestation. Through a case study on China's Twiplomacy in contesting coronavirus narrative in the UK, this paper further provides empirical evidence on how ‘networked transnational frame contestation' works between politically and culturally distant countries. Using a mixed-method approach combining social network analysis and discourse analysis, this study finds that China's emotion-evoking discursive strategy draws traction but the authoritarian nature of the highly centralised networkedness and that of its discursive strategy, together with the strong cultural discordance with British publics, lead to networked recontextualisation of its intended frames in Britain. British publics, heavily relying on British political elites and press for foreign affairs, invoke shared cultural reference to recontextualise Chinese frames into culturally resonant counterframes. This study proposes a paradigm of ‘networkedness within cascades' to understand frame contestation between politically and culturally distant countries. [ FROM AUTHOR]

Combination antiviral therapy with lopinavir/ritonavir, arbidol and interferon-α1b for COVID-19.

Since the outbreak of coronavirus disease (COVID-19) that was discovered in 2019 in Wuhan, China, no standard therapy guideline has been set despite the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its high infectivity. The globally pandemic outbreak suggests that COVID-19 is highly infectious and difficult to control. A dual-combination of ribavirin and interferon-α has been the widely used regimen for the treatment of this disease in China. However, due to the varying results of treatment with these drugs, a novel antiviral combination therapy is urgently needed. This case reports the usage of lopinavir/ritonavir-based combination antiviral regimen for a patient with SARS-CoV-2 infection.