Efficacy of Sofosbuvir plus Ledipasvir in Egyptian patients with COVID-19 compared to standard treatment: a randomized controlled trial.

COVID-19 is a pandemic disease caused by SARS-CoV-2, which is an RNA virus similar to the hepatitis C virus (HCV) in the replication process. Sofosbuvir/ledipasvir is an approved drug to treat HCV infection. This study investigates the efficacy of Sofosbuvir/ledipasvir as a treatment for patients with moderate COVID-19 infection. This is a single-blinded parallel-randomized controlled trial. The participants were randomized equally into the intervention group that received Sofosbuvir/ledipasvir (S.L. group), and the control group received Oseltamivir, Hydroxychloroquine, and Azithromycin (OCH group). The primary outcomes were the cure rate over time and the incidence of serious adverse events. The secondary outcomes included the laboratory findings. 250 patients were divided equally into each group. Both groups were similar regarding gender, but age was higher in the S.L. group (p=0.001). In the S.L. group, 89 (71.2%) patients were cured, while only 51 (40.8%) patients were cured in the OCH group. The cure rate was significantly higher in the S.L. group (RR=1.75, p<0.001). Kaplan-Meir plot showed a considerably higher cure over time in the S.L. group (Log-rank test, p=0.032). There were no deaths in the S.L. group, but there were six deaths (4.8%) in the OCH group (RR=0.08, p=0.013). Seven patients (5.6%) in the S.L. group and six patients (4.8%) in the OCH group were admitted to the intensive care unit (ICU) (RR=1.17, P=0.776). There were no significant differences between treatment groups regarding total leukocyte and neutrophils count, lymph, and urea. Sofosbuvir/ledipasvir is suggestive of being effective in treating patients with moderate COVID-19 infection. Further studies are needed to compare Sofosbuvir/ledipasvir with new treatment protocols.

Response Surface Methodology for Spectrophotometric Determination of Two ß-Adrenergic Agonists-Terbium Chemosensors in Urine and Pharmaceutical Dosage Forms.

BACKGROUND: According to literature reports, none of the previous methods of analysis had touched the multivariate approach for the quantification of significant factors affecting the interaction of dobutamine or hexoprenaline with Terbium. OBJECTIVE: Two novel ß-adrenergic agonists-lanthanide chemosensors were prepared for the determination of dobutamine and hexoprenaline in their pure and pharmaceutical dosage forms and in urine samples. Fabrication of the two chemosensors was based on their ligand-metal interaction with the lanthanide Terbium. METHODS: A Plackett-Burman Design (PBD) was selected for the screening of four main variables (reaction time, metal volume, pH, and temperature). Applying Response Surface Methodology (RSM), a Central Composite Design (CCD) was executed for the optimization of the significant factors with narrower upper and lower limits. Spectrophotometric technique was exploited for the analysis of the two chemosensors. RESULTS: Maximum absorption was obtained at 299 and 298 nm for dobutamine-terbium and hexoprenaline-terbium complexes, respectively. Only factors that were found to bear significant effects on the formed complexes were promoted to the optimization level. Model verification was carried out, where target results coincided with those at the predicted levels, indicating the efficiency of the two proposed models. Validation of the proposed was implemented and linear ranges were found to be 3.30-13.50 and 1.90-10.00 µg/mL, for dobutamine and hexoprenaline, respectively. CONCLUSIONS: Recovery and relative standard deviation values by application in pure powder, pharmaceutical dosage forms and spiked urine samples indicated high accuracy and reproducibility. Wide-ranging linear values and comparatively low detection limits inferred the effectiveness of the proposed method. HIGHLIGHTS: RSM for optimization of spectrophotometric determination of dobutamine and hexoprenaline ß-adrenergic agonists-lanthanide chemosensors; PBD was used for screening and CCD for optimization of variables affecting the spectrophotometric method; Determination of dobutamine and hexoprenaline in pure powder, pharmaceutical dosage form, and spiked urine samples was accomplished after method validation.

Design and optimization of a luminescent Samarium complex of isoprenaline: A chemometric approach based on Factorial design and Box-Behnken response surface methodology.

A chemometrically optimized procedure has been developed for the determination of isoprenaline (ISO) in the parent substance as well as in its respective pharmaceutical preparation. It is worth mentioning that although spectroscopic determination of Isoprenaline metal complexes has been described in literature, yet, no methods for the quantification of Isoprenaline with Samarium nor any other lanthanide metal have been reported. Fractional factorial design (FFD) was implemented in the initial screening procedure of the four designated factors, namely, reaction time (RT), metal volume (MV), pH and temperature (T) followed by Response Surface Methodology (RSM) optimization tool performed by the aid of Box Behnken design (BBD).The proposed techniques are based on a multivariate approach where a complexation reaction between Isoprenaline (ISO) and Samarium III (Sm3+) metal was exploited for the first time to synthesize novel fluorescence and absorbance probes of ISO-Sm. Maximum fluorescence intensity (Y1) as well as maximum absorbance (Y2) of the produced complex were attained at λex/λem = 315/450 and λ 295 nm for spectrofluorimetric and spectrophotometric determinations, respectively, against blank solutions. Using assessment quality tools such as, Pareto charts, normal probability plots and statistical analysis of variance testing (ANOVA), significant factors were successfully indicated (p < 0.05). Furthermore, the proposed methods verified specificity and accuracy for the determination of Isoprenaline in its pure and pharmaceutical preparation using spectrofluorimetric (Technique A) and spectrophotometric (Technique B) techniques, respectively. Linearity was obtained in the range of (0.02-0.50 µg/mL) and (2-12 µg/mL) upon employing both techniques A and B, respectively. Furthermore, limit of detection (LOD) and limit of quantification (LOQ), were found to be 5.1877 ∗ 10-3 µg/mL, 0.01572 µg/mL and 0.5593 µg/mL, 1.6949 µg/mL, upon employing techniques A and B, respectively. Standard addition method was applied for both techniques. The analysis was successfully applied to the assay of pure powder and pharmaceutical dosage forms after which the corresponding mean recoveries were computed and were found to be in the range of 99.546%-100.257% (Technique A) and 99.872%-99.887% (Technique B) with RSD (<1).

Plackett-Burman and Box-Behnken designs as chemometric tools for micro-determination of l-Ornithine.

Plackett-Burman (PB) and Box-Behnken (BB) screening and response surface factorial designs were used to evaluate spectrophotometric and spectrofluorimetric approaches for the determination of l-Ornithine (ORN) as per se and in dietary supplements. Both approaches were based on the derivatization of the primary amino group of ORN via Hantzsch condensation reaction producing yellow coloured adducts (dihydrolutidine derivative). The reaction product was determined spectrophotometrically (method A) at λmax=327nm and spectrofluorimetrically (method B) at 480nm (λem) after excitation at 325nm (λex). A multivariate scheme was tailored to investigate the process numerical variables; reaction temperature, heating time, reagent volume, and pH implementing PB as a screening design followed by BB as an optimization strategy. Categorical factors including diluting solvent and sequence of addition were kept invariable. Responses of the reaction systems were the maximum absorbance (Y1) and maximum fluorescence intensity (Y2), correspondingly. Quality tools as well as ANOVA testing, before and after response transformation were used to decide upon the substantial variables. Following the optimization of reaction variables using desirability plots, calibration graphs were found to be rectilinear in the range of 6-14µg/mL and 0.4-1.2µg/mL for methods A and B, respectively. Both methods proved to be sensitive with detection limits (DL) of 337 and 85ng/mL, and quantitation limits (QL) of 1086 and 283ng/mL, for methods A and B, respectively. An interference study was performed using potential foreign species. No significant interference effect was observed on any of the proposed procedures. System performance was addressed following ICH guidelines and considering parameters such as linearity, detection and quantification limits, accuracy and precision, robustness and specificity.

Potentiometric determination of tolterodine in batch and flow injection conditions.

Two new ion-selective electrodes of the plastic membrane type for the determination of Tolterodine (Tol) were prepared. These electrodes depend on the incorporation of the ion-exchangers of the above mentioned drug with phosphotungestic acid (PTA) or Silicotungestic acid (STA) in a PVC matrix. A comparative study is made between the performance characteristics of electrodes containing ion-exchanger in batch and FIA conditions. The usable concentration range of the electrodes was found to be (1.0×10(-5)-1.0×10(-2) and 5.0×10(-5)-1.0×10(-2)M) in batch and FIA conditions, respectively. The electrodes have nearly the same usable concentration, pH range and exhibited high selectivity toward Tol in the presence of many inorganic cations and can be used in biological fluids such as urine and plasma. The dissolution profile of the investigated drug as well as its assay in pure and pharmaceutical preparations was performed, and the results were relatively accurate and precise as indicated by the recovery values and coefficients of variation.