VALIDATED CHIRAL RP-UFLC METHOD FOR THE QUANTIFICATION OF CHLORTHALIDONE IN BULK AND PHARMACEUTICAL DOSAGE FORM

Objective: Development and validation of new, simple and reliable enantioselective reverse phase ultra-fast liquid chromatography (RP-UFLC) method for quantification of chlorthalidone in bulk and pharmaceutical dosage form.Methods: In the present study, the isocratic RP-UFLC method was developed on Phenomenex® Lux cellulose 4 column (250×4.6 mm, 5µ) and di-sodium hydrogen phosphate buffer (pH 3.6): methanol (40:60 v/v) as mobile phase. Elute was monitored at 240 nm with a flow rate of 1 ml/min.Results: The described method provided linear correlation (R2=0.999) between the range of 2-10 µg/ml. Chlorthalidone enantiomers showed good resolution with a retention time (tR) of 5.75 min and 7.46 min respectively. The precision of the method revealed that relative standard deviation is within the acceptable limit. The percentage recovery of each chlorthalidone enantiomers was found to be 99.98% and 100.09% respectively. The method was validated in accordance with ICH harmonized tripartite guidelines, validation of analytical procedures: text and methodology Q2 (R1).Conclusion: An economical, accurate, sensitive and precise RP-UFLC method was developed and fully validated for quality control analysis of chlorthalidone in pharmaceutical dosage form

Prevalence and predictors of seizure clusters: A prospective observational study of adult patients with epilepsy

Objective: The purpose of this prospective observational study was to describe the prevalence and adverse outcomes associated with seizure clusters (defined as >= 2 seizures in a 6-hour period) in a large sample of adult patients with a range of epilepsy severities and to identify clinical characteristics predictive of clustering. Methods: Patients maintained a seizure diary and were contacted monthly to verify compliance and data accuracy. Logistic regression models were utilized to test associations between individual patient demographic/clinical characteristics and seizure clustering. Fisher's exact test was utilized to test associations between rescue medication use and adverse seizure-related outcomes. Results: A total of 300 patientswere followed prospectively for one year; 247 patients qualified for final analysis. Six-hour seizure clusters occurred in 45.8% of patients with active epilepsy at enrollment, including 62.7% of thosewith prior day-clusters and 30.0% of thosewithout prior day-clusters. The odds of clusteringweremarkedly greater among patientswho reported a higher seizure frequency (>4 seizures per year vs. 1-4 seizures per year) (adjusted odds ratio (OR): 8.9; 95% confidence interval (CI): 3.2-24.6; p < 0.0001) and among patientswith prior day-clusters (adjusted OR: 11.0; 95% CI: 1.2-104.2; p=0.036). Rescue medication use was associated with significantly fewer injuries and emergency department visits, but rescue medication was underutilized. Conclusions: Seizure clusters are common, occurring in nearly half of adult patientswith active epilepsy followed prospectively over one year, and are more frequent in those with higher seizure frequencies and prior day-clusters. Although underutilized, rescue medication was associated with fewer injuries and emergency department visit. (c) 2018 Elsevier Inc. All rights reserved

Prospective assessment of ictal behavior using the revised Responsiveness in Epilepsy Scale (RES-II)

Impaired consciousness in epilepsy has a significant negative impact on patient quality of life, yet is difficult to study objectively. Here we develop an improved prospective Responsiveness in Epilepsy Scale (RES-II) and report initial results compared to the earlier version of the scale (RES). RES-II is simpler to administer and includes both verbal and nonverbal test items. We evaluated 75 seizures (24 patients) with RES and 34 seizures (11 patients) with RES-II based on video-EEG review. The error rate per seizure by test administrators improved markedly from a mean of 2.01±0.04 with RES to 0.24±0.11 with RES-II. Performance during focal seizures showed a bimodal distribution, corresponding to the traditional complex partial vs. simple partial seizure classification. We conclude that RES-II has improved accuracy and testing efficiency compared to the original RES. Prospective objective testing will ultimately lead to a better understanding of the mechanisms of impaired consciousness in epilepsy