Analytical Quality by Design Approach in RP-HPLC Method Development for the Assay of Etofenamate in Dosage Forms

By considering the current regulatory requirement for an analytical method development, a reversed phase high performance liquid chromatographic method for routine analysis of etofenamate in dosage form has been optimized using analytical quality by design approach. Unlike routine approach, the present study was initiated with understanding of quality target product profile, analytical target profile and risk assessment for method variables that affect the method response. A liquid chromatography system equipped with a C₁₈ column (250×4.6 mm, 5 μ), a binary pump and photodiode array detector were used in this work. The experiments were conducted based on plan by central composite design, which could save time, reagents and other resources. Sigma Tech software was used to plan and analyses the experimental observations and obtain quadratic process model. The process model was used for predictive solution for retention time. The predicted data from contour diagram for retention time were verified actually and it satisfied with actual experimental data. The optimized method was achieved at 1.2 ml/min flow rate of using mobile phase composition of methanol and 0.2% triethylamine in water at 85:15, % v/v, pH adjusted to 6.5. The method was validated and verified for targeted method performances, robustness and system suitability during method transfer.     

Associations between serum amino acids and incident type 2 diabetes in Chinese rural adults

Background and aimsSome amino acids (AAs) may be associated with type 2 diabetes (T2DM). This study aimed to determine the associations of individual AAs with the development of T2DM in rural Chinese adults.Methods and resultsA cohort study of 1199 individuals aged 18 years or older was conducted from 2006 to 2008 in a rural community of Deqing, China, a repeated survey was done in 2015 and data linkage with the electronic health records system was performed each year for identifying new T2DM cases. A high-performance liquid chromatography approach was used to measure the baseline serum concentrations of 15 AAs. Cox proportional hazards models were used to examine the associations between AAs and the risk of incident T2DM. A total of 98 new T2DM cases were identified during the follow-up of 12 years on average. Among 15 AAs, proline was associated with an increased risk of incident T2DM after adjusted for age, sex, body mass index, fasting plasma glucose, family history of T2DM, smoking status, alcohol use, and history of hypertension, the adjusted hazard ratio for 1-standard deviation increment was 1.20 (95% confidence interval: 1.00, 1.43). The association tended to be more marked in subjects younger than 60 years and overweight/obese subjects. Among participants without hypertension, proline and phenylalanine were associated with an increased risk of incident T2DM, while aspartic acid was associated with a decreased risk.ConclusionSerum proline was associated with the risk of incident T2DM in rural Chinese adults and might be a potential predictor.     

Efficacy and safety of warm acupuncture in the treatment of ankylosing spondylitis: A protocol for systematic review and meta-analysis

Background:Ankylosing spondylitis refers to a type of autoimmune disease, which is commonly characterized by joint pain and stiffness, since the disease progression can exhibit joint deformity and other activities limited symptoms. Has significantly impacts on people''s work and life. Warm acupuncture as a traditional Chinese therapy, showing several advantages (eg, safety, economy, and less side effects), has been extensively used to treat ankylosing spondylitis. However, its curative effect is supported by limited evidence. Accordingly, the present study aims to comprehensively assess the reliability of warm acupuncture in ankylosing spondylitis treatment.Methods:Randomized controlled trials were searched from the Chinese Biomedical Literature Database, Chongqing VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, Wanfang, Web of Science, Cochrane Library, PubMed, and EMBASE, regardless of their publication status. The deadline was November 6th, 2020. Two experienced researchers adopted RevMan V.5.3 software for literature selection, data collection, data analysis, and synthesis, respectively. In addition, the quality of the trials involved in this study was measured with the Cochrane Bias risk assessment tool, regardless of language or publication status.Results:The protocol will be used to assess the efficacy and safety of warm acupuncture in ankylosing spondylitis treatment.Conclusion:This review reliably evidences whether warm acupuncture is a reliable method for the intervention of ankylosing spondylitis.INPLASY registration number:INPLASY2020110096.     

复方黄柏液涂剂联合吲哚美辛栓治疗PPH术后肛门下坠

目的:观察复方黄柏液涂剂灌肠联合吲哚美辛栓纳肛治疗吻合器痔上黏膜环切术(Procedure for Prolapse and Hemorrhoids,PPH)术后肛门下坠的临床效果。方法:收集40例PPH术后1个月后出现肛门下坠患者并随机分为两组,治疗组20例,给予复方黄柏液涂剂灌肠联合吲哚美辛栓纳肛;对照组20例,单独给予吲哚美辛栓纳肛。7天为1个疗程,连续治疗2个疗程,观察治疗后的症状积分及治疗有效率。结果:两组患者治疗前肛门下坠评分比较,差异无统计学意义(P> 0.05);两组患者经过2个疗程的治疗,治疗前与治疗后的症状积分均有改善(P <0.05),2个疗程后治疗组的肛门下坠评分低于对照组(P <0.05)。治疗组总有效率为94.7%(18/19),低于对照组的78.9%(15/19),差异有统计学意义(P <0.05)。结论:复方黄柏液涂剂灌肠联合吲哚美辛栓治疗PPH术后肛门下坠比单独使用吲哚美辛栓效果明显,尤其是对肛门坠胀不适疼痛不明显者。     

Neutralising effects of small molecule toxin inhibitors on nanofractionated coagulopathic Crotalinae snake venoms

Repurposing small molecule drugs and drug candidates is considered as a promising approach to revolutionise the treatment of snakebite envenoming. In this study, we investigated the inhibiting effects of the small molecules varespladib (nonspecific phospholipase A₂ inhibitor), marimastat (broad spectrum matrix metalloprotease inhibitor) and dimercaprol (metal ion chelator) against coagulopathic toxins found in Crotalinae (pit vipers) snake venoms. Venoms from Bothrops asper, Bothrops jararaca, Calloselasma rhodostoma and Deinagkistrodon acutus were separated by liquid chromatography, followed by nanofractionation and mass spectrometry identification undertaken in parallel. Nanofractions of the venom toxins were then subjected to a high-throughput coagulation assay in the presence of different concentrations of the small molecules under study. Anticoagulant venom toxins were mostly identified as phospholipases A₂, while procoagulant venom activities were mainly associated with snake venom metalloproteinases and snake venom serine proteases. Varespladib was found to effectively inhibit most anticoagulant venom effects, and also showed some inhibition against procoagulant toxins. Contrastingly, marimastat and dimercaprol were both effective inhibitors of procoagulant venom activities but showed little inhibitory capability against anticoagulant toxins. The information obtained from this study aids our understanding of the mechanisms of action of toxin inhibitor drug candidates, and highlights their potential as future snakebite treatments.     

An eco-friendly HPLC-UV method for the determination of risedronate in its bulk and tablet dosage form with application to content uniformity,dissolution and stability testing

Risedronate is a nitrogen-containing bisphosphonate for the treatment and prevention of postmenopausal osteoporosis. The current work aims to develop a novel green HPLC-UV method for the rapid analysis of risedronate sodium in bulk and tablet formulation. The analyzed samples were separated on Waters Atlantis dC18 (150 mm × 3.9 mm; 5 μm) column using a green mobile phase consisting of potassium phosphate buffer pH 2.9 and potassium edetate buffer pH 9.5 in a ratio of 1:2, the final pH was adjusted to 6.8 with phosphoric acid, the mobile phase was pumped at a rate of 1.0 mL/min, with column temperature set at 30 °C, eluted samples were detected at 263 nm and the chromatographic run time was 3.0 min. The method was found to be linear over the concentration range of 14–140 μg/mL with a correlation coefficient (r²) of 0.9994. Accuracy and precision were evaluated from three QC samples (LQC, MQC and HQC) together with the five calibrators where the percentage accuracy was found to be 101.84%. Processed quality control samples of risedronate sodium were tested for stability at different conditions, short term, long term and freeze- thaw stability. The current method was further extended to study the content uniformity of Actonel® tablets following United States Pharmacopoeia (USP) guidelines. The proposed method was fully validated as per ICH guidelines.