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Carbon steel (CS) was pre-treated in CO 2 -saturated methyldiethanolamine (aq) to form FeCO 3 surface films, the protectiveness of which against corrosion in monoethanolamine was studied using electrochemical impedance spectroscopy, open circuit potential measurements and ex situ surface characterisation. Only pure, dense FeCO 3 films were found to provide protection in lab-scale tests. Dissolved O 2 in pre-treatment solutions resulted in traces of iron (hydr)oxide within the films, exacerbating non-uniform corrosion. Impure films were compromised in pilot-scale experiments in the CO 2 capture plant at Imperial College London. Therefore, pre-treating CS with methyldiethanolamine is not a robust corrosion control strategy for industrial CO 2 capture plants. • Pilot-scale stability tests of protective films formed through pre-treatment were conducted. • Pure FeCO 3 formed by pre-treating carbon steel was protective against corrosion in ethanolamine. • Dissolved O 2 in methyldiethanolamine resulted in iron oxide within the film. • Iron (hydr)oxide in surface films enhanced non-uniform corrosion in ethanolamine. • Pre-treatment with methyldiethanolamine should not be used for corrosion control. [ABSTRACT FROM AUTHOR]

Favipiravir is a broad-spectrum antiviral that is metabolised intracellularly into the active form, favipiravir ribofuranosyl-5'-triphosphate (F-RTP). Measurement of the intracellular concentration of F-RTP in mononuclear cells is a crucial step to characterising the pharmacokinetics of F-RTP and to enable more appropriate dose selection for the treatment of COVID-19 and emerging infectious diseases. The described method was validated over the range 24 – 2280 pmol/sample. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and lysed using methanol-water (70:30, v/v) before cellular components were precipitated with acetonitrile and the supernatant further cleaned by weak anion exchange solid phase extraction. The method was found to be both precise and accurate and was successfully utilised to analyse F-RTP concentrations in patient samples collected as part of the AGILE CST-6 clinical trial. • A simple, sensitive assay for quantification of T-705 RTP (F-RTP) in human PBMC. • Direct quantification of the active intracellular favipiravir metabolite (F-RTP). • Whole blood instability of F-RTP at room temperature for 1 h. • Method successfully applied to clinical samples as part of the AGILE CST-6 trial. [ABSTRACT FROM AUTHOR]

Favipiravir (FVP) is a broad-spectrum antiviral that selectively inhibits viral RNA-dependent RNA polymerase, first trialled for the treatment of influenza infection. It has been shown to be effective against a number of RNA virus families including arenaviruses, flaviviruses and enteroviruses. Most recently, FVP has been investigated as a potential therapeutic for severe acute respiratory syndrome coronavirus 2 infection. A liquid chromatography tandem mass spectrometry method for the quantification of FVP in human plasma has been developed and validated for use in clinical trials investigating favipiravir as treatment for coronavirus disease-2019. Samples were extracted by protein precipitation using acetonitrile, using 13C, 15N- Favipiravir as internal standard. Elution was performed on a Synergi Polar-RP 150 × 2.1 mm 4 µm column using a gradient mobile phase programme consisting of 0.2% formic acid in water and 0.2% formic acid in methanol. The assay was validated over the range 500–50,000 ng/mL; this method was found to be precise and accurate and recovery of FVP from the matrix was high. Stability experiments confirmed and expanded on the known stability of FVP, including under heat treatment and for a period of 10 months at − 80 °C. • A fully validated, simple, robust assay for quantification of favipiravir in human plasma. • Favipiravir is stable for up to four rounds of heat inactivation at 58 °C for 40 min. • Long term stability of favipiravir established at 10 months for plasma stored at − 80 °C. • Method successfully applied to clinical samples as part of the AGILE CST-6 clinical trial. [ABSTRACT FROM AUTHOR]

Background: The antiviral drug molnupiravir was licensed for treating at-risk patients with COVID-19 on the basis of data from unvaccinated adults. We aimed to evaluate the safety and virological efficacy of molnupiravir in vaccinated and unvaccinated individuals with COVID-19.Methods: This randomised, placebo-controlled, double-blind, phase 2 trial (AGILE CST-2) was done at five National Institute for Health and Care Research sites in the UK. Eligible participants were adult (aged ≥18 years) outpatients with PCR-confirmed, mild-to-moderate SARS-CoV-2 infection who were within 5 days of symptom onset. Using permuted blocks (block size 2 or 4) and stratifying by site, participants were randomly assigned (1:1) to receive either molnupiravir (orally; 800 mg twice daily for 5 days) plus standard of care or matching placebo plus standard of care. The primary outcome was the time from randomisation to SARS-CoV-2 PCR negativity on nasopharyngeal swabs and was analysed by use of a Bayesian Cox proportional hazards model for estimating the probability of a superior virological response (hazard ratio [HR]>1) for molnupiravir versus placebo. Our primary model used a two-point prior based on equal prior probabilities (50%) that the HR was 1·0 or 1·5. We defined a priori that if the probability of a HR of more than 1 was more than 80% molnupiravir would be recommended for further testing. The primary outcome was analysed in the intention-to-treat population and safety was analysed in the safety population, comprising participants who had received at least one dose of allocated treatment. This trial is registered in ClinicalTrials.gov, NCT04746183, and the ISRCTN registry, ISRCTN27106947, and is ongoing.Findings: Between Nov 18, 2020, and March 16, 2022, 1723 patients were assessed for eligibility, of whom 180 were randomly assigned to receive either molnupiravir (n=90) or placebo (n=90) and were included in the intention-to-treat analysis. 103 (57%) of 180 participants were female and 77 (43%) were male and 90 (50%) participants had received at least one dose of a COVID-19 vaccine. SARS-CoV-2 infections with the delta (B.1.617.2; 72 [40%] of 180), alpha (B.1.1.7; 37 [21%]), omicron (B.1.1.529; 38 [21%]), and EU1 (B.1.177; 28 [16%]) variants were represented. All 180 participants received at least one dose of treatment and four participants discontinued the study (one in the molnupiravir group and three in the placebo group). Participants in the molnupiravir group had a faster median time from randomisation to negative PCR (8 days [95% CI 8-9]) than participants in the placebo group (11 days [10-11]; HR 1·30, 95% credible interval 0·92-1·71; log-rank p=0·074). The probability of molnupiravir being superior to placebo (HR>1) was 75·4%, which was less than our threshold of 80%. 73 (81%) of 90 participants in the molnupiravir group and 68 (76%) of 90 participants in the placebo group had at least one adverse event by day 29. One participant in the molnupiravir group and three participants in the placebo group had an adverse event of a Common Terminology Criteria for Adverse Events grade 3 or higher severity. No participants died (due to any cause) during the trial.Interpretation: We found molnupiravir to be well tolerated and, although our predefined threshold was not reached, we observed some evidence that molnupiravir has antiviral activity in vaccinated and unvaccinated individuals infected with a broad range of SARS-CoV-2 variants, although this evidence is not conclusive.Funding: Ridgeback Biotherapeutics, the UK National Institute for Health and Care Research, the Medical Research Council, and the Wellcome Trust. [ABSTRACT FROM AUTHOR]

Abstract: Horizontal flows of two immiscible liquids with the same refractive index, a kerosene-like hydrocarbon and a glycerol–water solution, have been instigated with planar laser-induced fluorescence in a square duct. Four flow regime categories were observed, these being: (1) stratified flow; (2) mixed flow (i.e., two distinct continuous phase regions with droplets in each); (3) two-layer flow, comprised of a dispersed region and a continuous, unmixed region (i.e., oil-dispersed flow over glycerol solution flow and, oil flow over a glycerol solution dispersion); and (4) dispersed flows (i.e., continuous oil phase dispersion and continuous glycerol solution dispersion. The flow can be described as occupying three zones; an oil phase at the top, a glycerol–water phase at the bottom, with a mixed zone between them. The vertical height covered by the mixed zone increased for increasing superficial mixture velocity, and the vertical height of the glycerol–water phase decreased for increasing input oil fraction. At low oil fractions the interface level separating the two phases was not affected by changes to the superficial mixture velocity. However, at higher oil fractions the interface height from the bottom of the channel decreased progressively as the superficial velocity was increased. Higher velocities also gave rise to increasingly fluctuating interface level heights. The mean droplet size increased initially, reached a maximum and then decreased as the oil fraction was increased, and was largest at intermediate and smallest at high superficial velocities. [Copyright &y& Elsevier]

Abstract: A series of two-phase air–water experiments was carried out in order to study the initiation and the subsequent evolution of hydrodynamic slugs in a horizontal pipeline. Experiments were carried out at atmospheric pressure, 4.0bar(a) and 9.0bar(a), and the effects of superficial liquid and gas velocities were investigated. The test section used for these experiments is 37m in length, with an internal diameter of 0.078m. To study the interfacial development, measurements of interfacial structures were made at 14 axial locations along the test section, with data acquired at a sampling frequency of 500Hz. A large number of slugs were initiated within the first 3m of the test section, with the frequency subsequently reducing towards the fully developed value before the end of the pipe. This reduction in frequency was strongly influenced by the magnitude of the gas and liquid velocities. The frequency of slugging was not strongly affected when the system pressure was changed from 1 atmosphere, to 4.0 and 9.0bar(a), closely similar values being obtained at the 10 downstream locations. However, higher pressure delayed the onset of slug initiation, with “slug precursors” being formed further downstream as the pressure was increased. The statistical distributions of slug lengths and of the time intervals between slug arrivals were examined in detail and compared to several standard distributions. This showed that slug initiation may be reasonably approximated as an uncorrelated Poisson process with an exponential distribution of arrival times. However, once slugs have developed, there is strong correlation and the arrival time intervals, as well as the lengths, are best represented by the log-normal distribution. [Copyright &y& Elsevier]

• A fully developed and validated LC-MS/MS method for simultaneous detection of MPV & NHC in plasma & saliva. • Sample preparation involved stabilising the plasma and saliva samples using acetonitrile. • MPV was mostly unquantifiable in plasma and saliva while NHC was quantifiable throughout. • The method is sensitive with LOQ of 2.5 ng/ml and saliva/plasma ratio was 0.12 ± 0.27 (Mean±SD). • This novel LC-MS method can be applied to other COVID-19 PK studies using the same drugs. In light of the recent global pandemic, Molnupiravir (MPV) or EIDD-2801, developed for the treatment of patients with uncomplicated influenza, is now being trialled for the treatment of infections caused by highly pathogenic coronaviruses, including COVID-19. A sensitive LC-MS/MS method was developed and validated for the simultaneous quantification of MPV and its metabolite ß-d-N4-hydroxycytidine (NHC) in human plasma and saliva. The analytes were extracted from the matrices by protein precipitation using acetonitrile. This was followed by drying and subsequently injecting the reconstituted solutions onto the column. Chromatographic separation was achieved using a polar Atlantis C 18 column with gradient elution of 1 mM Ammonium acetate in water (pH4.3) and 1 mM Ammonium acetate in acetonitrile. Analyte detection was conducted in negative ionisation mode using SRM. Analysis was performed using stable isotopically labelled (SIL) internal standards (IS). The m/z transitions were: MPV (328.1→126.0), NHC (258.0→125.9) and MPV-SIL (331.0→129.0), NHC-SIL (260.9→128.9). Validation was over a linear range of 2.5–5000 ng/ml for both plasma and saliva. Across four different concentrations, precision and accuracy (intra- and inter-day) were 15%; and recovery of both analytes from plasma and saliva was between 95% and 100% and 65–86% respectively. Clinical pharmacokinetic studies are underway utilising this method for determination of MPV and its metabolite in patients with COVID-19 infection. [ABSTRACT FROM AUTHOR]