Consensus Guideline on the Management of Epilepsy in Egypt: A National Delphi Consensus Study.

OBJECTIVE: In epilepsy, early diagnosis, accurate determination of epilepsy type, proper selection of antiseizure medication, and monitoring are all essential. However, despite recent therapeutic advances and conceptual reconsiderations in the classification and management of epilepsy, serious gaps are still encountered in day-to-day practice in Egypt as well as several other resource-limited countries. Premature mortality, poor quality of life, socio-economic burden, cognitive problems, poor treatment outcomes, and comorbidities are major challenges that require urgent actions to be implemented at all levels. In recognition of this, a group of Egyptian epilepsy experts met through a series of consecutive meetings to specify the main concepts concerning the diagnosis and management of epilepsy, with the ultimate goal of establishing a nationwide Egyptian consensus. METHODS: The consensus was developed through a modified Delphi methodology. A thorough review of the most recent relevant literature and international guidelines was performed to evaluate their applicability to the Egyptian situation. Afterward, several remote and live rounds were scheduled to reach a final agreement for all listed statements. RESULTS: Of 278 statements reviewed in the first round, 256 achieved ≥80% agreement. Live discussion and refinement of the 22 statements that did not reach consensus during the first round took place, followed by final live voting then consensus was achieved for all remaining statements. SIGNIFICANCE: With the implementation of these unified recommendations, we believe this will bring about substantial improvements in both the quality of care and treatment outcomes for persons with epilepsy in Egypt. PLAIN LANGUAGE SUMMARY: This work represents the efforts of a group of medical experts to reach an agreement on the best medical practice related to people with epilepsy based on previously published recommendations while taking into consideration applicable options in resource-limited countries. The publication of this document is expected to minimize many malpractice issues and pave the way for better healthcare services on both individual and governmental levels.

Stability-indicating RP-HPLC assay of three novel oral anticoagulants binary mixtures with rosuvastatin calcium: Application to pharmaceutical preparations and human plasma.

The binary mixtures of the novel oral anticoagulants (NOACs); Apixaban (APX), Edoxaban tosylate (EDX) and Rivaroxaban (RIV) with the lipid lowering statin; Rosuvastatin calcium were analyzed using a validated HPLC-DAD method. This method was suitable for the quantitative assay of the targeted mixtures in tablets and human plasma. The analysis in dosage form was a stability indicating one where the drugs were separated from possible degradation products arising from applying different stress conditions. For analysis in human plasma, EDX was used as internal standard in APX/ROS and RIV/ROS mixtures, while APX was used as internal standard in EDX/ROS mixture and the method was validated according to FDA regulation for analysis in biological fluids. A ZORBAX Eclipse column C18 (4.6 × 150 mm × 5 µm) was used as stationary phase with a gradient eluting mobile phase composed of acidified water and acetonitrile. The method selectivity was demonstrated by its ability to simultaneously analyze the drugs in presence of possible forced degradation products and dosage form excipients and in presence of plasma interferences (analysis in biological fluid) at a single wavelength (291 nm) with the use of the internal standard. The simplicity of the method emphasizes its capability to analyze the drugs in pharmaceutical preparations and human plasma. This is very important in regular clinical monitoring of the drugs plasma concentrations for cardiovascular patients medicated with either of these combinations, as prophylaxis from stroke, in order to prevent severe bleeding and to achieve optimum dose adjustment.

Comparative Greenness Metric Estimates for Content Uniformity Testing of Anti-Cov-2, GS-5734 in Commercial Vials: Validated Micellar Electrokinetic Chromatographic Assay.

BACKGROUND: The antiviral drug GS-5734 remdesivir is a new phosphoramidate prodrug developed initially as a treatment for Ebola virus which then proved to have antiviral properties against other viruses. After clinical trials, it was the first antiviral to be approved by the U.S. Food and Drug Administration in 2020 to treat severe coronavirus (COVID-19) cases. The widespread current pandemic gave an urge to its fast production and marketing. Thus, new analytical methods must be available for its analysis in a fast and easy manner with low cost to be applicable in all laboratories. OBJECTIVE: In the current study, a green and economic micellar electrokinetic chromatographic (MEKC) method is proposed for remdesivir analysis. METHODS: A fused-silica capillary (58.5 cm × 50 µm id, 50 cm effective length) with 20 mM borate buffer (pH 9) and 25 mM sodium dodecyl sulfate was used under a positive potential of 30 kV at 25°C with detection at 245 nm. RESULTS: Remdesivir analysis was achieved in approximately 5 min. The method proved to be linear in range of 1-50 µg/mL with correlation coefficient, r > 0.999. CONCLUSION: The MEKC method proposed was applied to the analysis of remdesivir in its commercial vials. The method was validated per International Conference on Harmonization guidelines. HIGHLIGHTS: Green chemistry has been the focus of the analytical community in the past few years. This method is considered green due to its low energy and solvent consumption without sacrificing the method's sensitivity or selectivity. The method's green profile has been assessed by different greenness assessment scales to ensure the method is eco-friendly and can be used in the pharmaceutical industry.

Accelerated stability study of the ester prodrug remdesivir: Recently FDA-approved Covid-19 antiviral using reversed-phase-HPLC with fluorimetric and diode array detection.

Remdesivir (RDV) is the first antiviral drug, approved by the Food and Drug Administration, to treat severe acute respiratory syndrome coronavirus 2. RDV is a relatively new chemical entity, 'ester prodrug', with no reported stability profile. Due to the urgency of its use and thus fast production, it is important to develop a stability-indicating method for its assay. Chromatographic separation was carried out on a C18 column (250 × 4.6 mm, 5 µm) with dual detection: diode array at 240 nm and fluorescence at λex/em 245/390 nm. Isocratic elution of acetonitrile and distilled water (acidified with phosphoric acid, pH 4) in the ratio of 55:45 (v/v), respectively, was used. The linearity range using HPLC-diode array detection was 0.1-15 µg/mL, whereas that using fluorimetric detection was 0.05-15 µg/mL. As per the International Conference on Harmonization guidelines, RDV has been degraded by accelerated alkaline, acidic, neutral hydrolysis, oxidative, heat, and photolytic stress conditions. Possible degradation hypothesis of the parent molecule has been suggested and illustrated. The proposed methods have achieved selective determination of the intact drug with no peaks overlapping in all assumptions. Extensive degradation confirms threatened drug stability at thermal and basic hydrolytic stressing. The developed methods were fully validated and proved suitable for quality control routine analysis of RDV in raw material and pharmaceutical dosage forms.

Green spectrofluorimetric methods for tramadol assay with ibuprofen or chlorzoxazone: comparison of greenness profiles.

At this time, green analytical chemistry is gaining more interest and concern. The present work details three green spectrofluorimetric methods for tramadol (TRM) determination using ibuprofen (IBU) (mixture 1) and chlorzoxazone (CLZ) (mixture 2). In first method, two excitation wavelengths (λex ), 220 and 280 nm, were used to record the emission spectra for IBU and TRM, respectively (mixture 1) followed by a first derivative treatment. For mixture 2, one λex (280 nm) was optimum for both drugs followed by a first derivative technique for TRM and a second derivative for CLZ determinations. The second method measured the first derivative values for synchronous spectra using constant-wavelength mode at 280 nm for TRM and 260 nm for IBU, and at 270 nm for TRM and 292 nm for CLZ. The third method used constant-energy mode to record synchronous spectra. First derivative values were computed at 282 nm for TRM and 260 nm for IBU in mixture 1 and at 272 nm for TRM and 292 nm for CLZ in mixture 2. ICH validation guidelines were assessed in full and assay of the two TRM binary mixtures in their drug products was successful. Green profile evaluation for the developed methods compared with the reported chromatographic methods was performed using the 'analytical eco-scale' and the 'green analytical procedure index'. These two assessment tools corroborated that the proposed methods achieved the most green parameters, therefore recommending their use as a green option for analyzing the studied drugs in bulk and dosage forms for routine quality control.

Rapid eye movement (REM) sleep and seizure control in idiopathic generalized epilepsy.

BACKGROUND: Sleep and epilepsy are bedfellows, and they affect each other reciprocally. Despite the well-known relationship between sleep and epilepsy, data about the impact of sleep on seizure control and responsiveness to therapy are scarce. OBJECTIVE: The aim of this work was to study the impact of sleep architecture in drug-naïve patients with idiopathic generalized epilepsy (IGE) on seizure control and responsiveness to treatment. METHODS: This is a prospective cohort study conducted on thirty newly diagnosed patients with IGE attending the epilepsy clinic in Alexandria University Hospital in Egypt and thirty healthy controls. All recruited subjects had a baseline overnight polysomnographic study, then patients were given sodium valproate in therapeutic doses and followed up for six months for assessment of seizure control. After follow-up, they were classified into fully controlled and inadequately controlled patients, and a comparison between them was made. RESULTS: Of the recruited patients, 13 were fully controlled. Rapid eye movement (REM) sleep % was significantly lower among inadequately controlled patients (9.01 ±â€¯6.23) than fully controlled group (19.6 ±â€¯9.01) and controls (18.17 ±â€¯4.85) (p = 0.002), and the REM sleep latency was significantly longer among the inadequately controlled patients (115.7 ±â€¯72.8 min) than fully controlled patients (54.6 ±â€¯77.3 min) and controls (68.75 ±â€¯37.95 min) (p = 011). On univariate regression analysis, the Odd's ratio (OR) for REM sleep percentage was 3.04 (p = 0.001). CONCLUSION: Rapid eye movement sleep percentage and latency can contribute to seizure control in IGE.

Stability indicating HPLC-DAD method for analysis of Ketorolac binary and ternary mixtures in eye drops: Quantitative analysis in rabbit aqueous humor.

Ketorolac tromethamine (KTC) with phenylephrine hydrochloride (PHE) binary mixture (mixture 1) and their ternary mixture with chlorpheniramine maleate (CPM) (mixture 2) were analyzed using a validated HPLC-DAD method. The developed method was suitable for the in vitro as well as quantitative analysis of the targeted mixtures in rabbit aqueous humor. The analysis in dosage form (eye drops) was a stability indicating one at which drugs were separated from possible degradation products arising from different stress conditions (in vitro analysis). For analysis in aqueous humor, Guaifenesin (GUF) was used as internal standard and the method was validated according to FDA regulation for analysis in biological fluids. Agilent 5 HC-C18(2) 150×4.6mm was used as stationary phase with a gradient eluting solvent of 20mM phosphate buffer pH 4.6 containing 0.2% triethylamine and acetonitrile. The drugs were resolved with retention times of 2.41, 5.26, 7.92 and 9.64min for PHE, GUF, KTC and CPM, respectively. The method was sensitive and selective to analyze simultaneously the three drugs in presence of possible forced degradation products and dosage form excipients (in vitro analysis) and also with the internal standard, in presence of aqueous humor interferences (analysis in biological fluid), at a single wavelength (261nm). No extraction procedure was required for analysis in aqueous humor. The simplicity of the method emphasizes its capability to analyze the drugs in vivo (in rabbit aqueous humor) and in vitro (in pharmaceutical formulations).

Development and Validation of a High-Performance Thin-Layer Chromatographic Method for the Simultaneous Determination of Two Binary Mixtures Containing Ketorolac Tromethamine with Phenylephrine Hydrochloride and with Febuxostat.

A validated and highly selective high-performance thin-layer chromatography (HPTLC) method was developed for the determination of ketorolac tromethamine (KTC) with phenylephrine hydrochloride (PHE) (Mixture 1) and with febuxostat (FBX) (Mixture 2) in bulk drug and in combined dosage forms. The proposed method was based on HPTLC separation of the drugs followed by densitometric measurements of their spots at 273 and 320 nm for Mixtures 1 and 2, respectively. The separation was carried out on Merck HPTLC aluminum sheets of silica gel 60 F254 using chloroform-methanol-ammonia (7:3:0.1, v/v) and (7.5:2.5:0.1, v/v) as mobile phase for KTC/PHE and KTC/FBX mixtures, respectively. Linear regression lines were obtained over the concentration ranges 0.20-0.60 and 0.60-1.95 µg band(-1)for KTC and PHE (Mixture 1), respectively, and 0.10-1.00 and 0.25-2.50 µg band(-1) for KTC and FBX (Mixture 2), respectively, with correlation coefficients higher than 0.999. The method was successfully applied to the analysis of the two drugs in their synthetic mixtures and in their dosage forms. The mean percentage recoveries were in the range of 98-102%, and the RSD did not exceed 2%. The method was validated according to ICH guidelines and showed good performances in terms of linearity, sensitivity, precision, accuracy and stability.