Development and validation of a versatile HPLC-DAD method for simultaneous determination of the antiviral drugs daclatasvir,ledipasvir, sofosbuvir and ribavirin in presence of seven potential impurities. Application to assay of dosage forms and dissolution studies

This study describes a simple, sensitive, specific and generic HPLC-DAD method for simultaneous determination of four drugs prescribed for treatment of Hepatitis C Virus (HCV) infection. Investigated drugs include daclatasvir (DAC), ledipasvir (LED), sofosbuvir (SOF) and ribavirin (RIB). Successful separation was accomplished using Thermohypersil BDS-C8 column (4.6?×?250?mm, 5?µm) with gradient elution of the mobile phase consisted of mixed phosphate buffer pH 7.5 and methanol. Gradient elution started with 25% methanol, ramped up linearly to 80% in 15?min then kept constant till the end of the run. Flow rate was 1.5?mL/min. Peak areas were measured at 235, 260, 315, and 332?nm for RIB, SOF, DAC, and LED, respectively. Peaks of the analytes were perfectly resolved with retention times 2.0, 12.1, 14.7, and 17.2?min for RIB, SOF, DAC, and LED, respectively. The developed method was validated according to ICH guidelines with respect to system suitability, linearity, ranges, accuracy, precision, specificity, robustness, and limits of detection and quantification. The proposed method showed good linearity in the ranges 5–500, 2–300, 0.5–75, and 0.5–75?µg/mL for RIB, SOF, DAC, and LED respectively. Limits of detection were 0.10–0.66?μg/mL for the analyzed drugs. Specificity was established by separation of target drugs from 7 process-related impurities for SOF including its major metabolite (GS-331007). Applicability of the proposed method to real life situations was assessed through the analysis of four different pharmaceutical formulations and satisfactory results were obtained. Additionally, dissolution profiles of the 4 drugs were studied using the developed method.     

Fitness-to-drive after mild traumatic brain injury: Mapping the time trajectory of recovery in the acute stages post injury

Introduction

Little is known about the trajectory of recovery in fitness-to-drive after mild traumatic brain injury (mTBI). This means that health-care professionals have limited evidence on which to base recommendations to this cohort about driving.

Objective

To determine fitness-to-drive status of patients with a mTBI at 24 h and two weeks post injury, and to summarise issues reported by this cohort about return to driving.

Method

Quasi-experimental case-control design. Two groups of participants were recruited: patients with a mTBI (n = 60) and a control group with orthopaedic injuries (n = 60). Both groups were assessed at 24 h post injury on assessments of fitness-to-drive. Follow-up occurred at two weeks post injury to establish driver status.

Main Measures

Mini mental state examination, occupational therapy-drive home maze test (OT–DHMT), Road Law Road Craft Test, University of Queensland-Hazard Perception Test, and demographic/interview form collected at 24 h and at two weeks.

Results

At the 24 h assessment, only the OT–DHMT showed a difference in scores between the two groups, with mTBI participants being significantly slower to complete the test (p = 0.01). At the two week follow-up, only 26 of the 60 mTBI participants had returned to driving. Injury severity combined with scores from the 24 h assessment predicted 31% of the variance in time taken to return to driving. Delayed return to driving was reported due to: “not feeling 100% right” (n = 14, 23%), headaches and pain (n = 12, 20%), and dizziness (n = 5, 8%).

Conclusion

This research supports existing guidelines which suggest that patients with a mTBI should not to drive for 24 h; however, further research is required to map factors which facilitate timely return to driving.     

Thermodynamic limits to thermal regeneration in adsorption cooling cycles

Energy and exergy models for ideal adsorption cycles with isothermal beds and no mass recovery are developed to predict the limits to COP enhancement using thermal regeneration. The models are applied to compare the performance of zeolite–water and silica gel–water adsorbent–refrigerant pairs over a range of maximum bed temperatures. The thermodynamic consistencies of several alternate adsorption property assumptions are quantified. Differences in adsorption characteristics between zeolite–water and silica gel–water result in a significantly larger potential to enhance COP by implementing thermal regeneration for zeolite–water. Based on COP, the zeolite–water pair is preferred when both thermal regeneration and a high temperature thermal energy source (>150 °C) are used, while the silica gel–water pair is preferred when thermal regeneration is not used and/or a low temperature thermal energy source (<100 °C) is used.     

Analysis and Compression Testing of Laminates Optimised for Damage Tolerance

Barely Visible Impact Damage (BVID) can occur when laminated composite material is subject to out-of-plane impact loads and can result in a significant reduction in compressive strength. This paper reports on three compression tests of laminates optimised to maximise damage tolerance. Results from these tests were analysed using a semi-analytical, fracture mechanics based method that predicts the strain below which laminated coupons containing BVID subject to axial compression will not fail. A further experiment was conducted on an artificially delaminated coupon in order to validate the modelling methodology. Results from one of the two optimised stacking sequences considered show an increase of over 40% in Compression After Impact (CAI) strength compared with a baseline configuration. Analysis of results has indicated that CAI strength is dependent to a great extent on damage morphology and stability of damage growth, both of which are functions of laminate stacking sequence.     

Alcohol use in relation to driving records among injured bicyclists

To prevent alcohol-related occupational mishaps, employers often conduct background checks on prospective employees for history of driving while intoxicated (DWI) and driving under the influence of alcohol (DUI) to screen out candidates with drinking problems. Few studies, however, have examined the pervasive nature of drinking behavior across activity domains. Based on trauma registry data, we constructed a historical cohort of 120 Maryland residents ages 18 years or older who were injured while riding a bicycle between 1990 and 1997. Driving records for the 120 bicyclists for the 3 years between May 6, 1995 and May 5, 1998 were obtained from the state motor vehicle administration and were analyzed in relation to BAC-positive status at the time of injury. Bicyclists with positive BACs at the time of admission to the trauma center were significantly more likely than those with negative BACs to have a record of license suspension/revocation (52% vs 14%, P < 0.01) and to have DWI/DUI convictions (30% vs 3%, P < 0.01). Despite the modest sample size, this study provides compelling evidence of the pervasive nature of risky drinking between bicycling and driving activities.     

Genetic risk factors for disordered eating in adolescent males and females.

The etiologic role of genetic and environmental factors on disordered eating was examined in a sample of 15- to 17-year-old female–female, male–male, and opposite-sex twin pairs. Also assessed was whether a single factor is underlying 3 facets (body dissatisfaction, drive for thinness, bulimia) of disordered eating, including the possible importance of sex differences. Univariate model-fitting analyses indicated that genetic factors are more important for girls and environment more important for boys for body dissatisfaction and drive for thinness. A multivariate common factor analysis indicated that a single factor accounted for the association among these 3 facets of disordered eating in both sexes. However, only 50% of the genetic risk for this factor is shared between the sexes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

News & notes.

Provides news and information for the members of the American Psychological Association Division 26 members. (PsycINFO Database Record (c) 2010 APA, all rights reserved)