Using HPLC to analyze (S)-oxiracetam and four related substances in the bulk drug of (S)-oxiracetam.

(S)-oxiracetam is undergoing clinical trials as an active ingredient in the racemic oxiracetam. Here, we report a specific analytical method for analyzing (S)-oxiracetam and four related impurities in the bulk drug of (S)-oxiracetam by using high-performance liquid chromatography (HPLC) system. The chromatographic system included a Capcell pak NH2 analytical column, a mobile phase containing acetonitrile-water (95:5, v/v; pH adjusted to 2.0 with trifluoroacetic acid) at a flow rate of 1.0 mL/min, column temperature at 35 ℃ and the UV detection wavelength is set at 210 nm. This analytical method has shown effective and specific analysis for (S)-oxiracetam and four related substances. Moreover, the molecular weight and chemical structure preliminarily speculated of related substances were characterized by mass spectrometry. The methodology was verified by HPLC and results collected of the method validation included the system suitability, specificity sensitivity, linearity and accuracy, good linear correlation coefficient R2 was more than 0.9991. The analytical method developed and verified in the study, as far as we know, is the most exhaustive HPLC determination report which could be applied for the quality control and stability monitor purposes of the bulk drug of (S)-oxiracetam in the routine pharmaceutical analysis.

Microbial Contamination of Rigid Gas Permeable (RGP) Trial Lenses and Lens Cases in China.

Purpose: This study aimed to evaluate the microbial contamination level and its influencing factors of rigid gas permeable (RGP) trial lenses and lens cases in China.Materials and Methods: A total of 107 RGP trial lenses and lens cases were collected from 7 main hospitals or optometric centers in China. Three sites including the lenses, case interiors and case screw tops were sampled for bacterial and fungal culture and identification. The contamination rates of these three sites and their relationship with lens care regimes were further analyzed.Results: The overall contamination rate was 73.8% for either lenses or cases, and 43.0% of lenses, 57.0% of case interiors and 65.4% of case screw tops respectively. The most frequently isolated microorganisms were Serratia spp., Burkholderia spp., Pandoraea spp., and Achromobacter spp. from all three sites. The contamination rate was positively related to the lens use frequency. Compared with dry-stored lenses, the contamination rate was significantly higher in wet-stored group (P < .001*). Inadequate disinfection and improper lens and case care regimes were also associated with higher contamination rates.Conclusions: Our study reported that the RGP trial lenses and cases used for fittings had a considerably high contamination rate. The safe use of RGP trial lenses and education of optometrists on the regular maintenance of trial lenses should be emphasized.

Efficacy and safety of evocalcet in treatment of secondary hyperparathyroidism in chronic kidney disease on hemodialysis patients: A protocol for a systematic review and meta-analysis.

BACKGROUND: Secondary hyperparathyroidism (SHPT) have been associated with poor health outcomes in hemodialysis patients. The cinacalcet has popularized in clinic which has efficacy but more adverse events; the novel oral calcimimetic agents evocalcet has appeared in recent years. However, it is currently unknown whether evocalcet produces more beneficial effects and fewer adverse events in patients with SHPT. The aim of this systematic review is to estimate the safety and efficacy of evocacelt. METHODS: Only randomized controlled trials (RCT) will be included in MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, and PUBMED from July 2010 to July 2020. Two reviewers will screen, select studies, extract data, and assess quality independently. The methodological quality including the risk of bias of the included studies will be evaluated using a modified assessment form, which is based on Cochrane assessment tool. Review Manager 5.3 software will be used for heterogeneity assessment, generating funnel-plots, data synthesis, subgroup analysis, and sensitivity analysis. We will use GRADE system to evaluate the quality of our evidence. RESULTS: We will provide some more practical and targeted results investigating the effect and safety of evocalcet for SHPT on hemodialysis in the current meta-analysis. CONCLUSION: The stronger evidence about evocalcet effect and safety will be provided for clinicians and policymakers. ETHICS AND DISSEMINATION: Ethical approval will be unnecessary because the data being included in this systematic review come from published literature and there will be no concerns regarding privacy. Findings of this research will be disseminated in a peer-reviewed journal or conference presentations. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/N59RB.

Toxicokinetic evaluation of atrasentan in mice utilizing serial microsampling: validation and sample analysis in GLP study.

BACKGROUND: A semi-automated 96-well protein precipitation followed by HPLC-MS/MS method for the determination of atrasentan (2R-[4-methoxyphenyl]-4S-[1,3-benzodioxol-5-yl]-1-[N,N-di-(N-butyl)-aminocarbonyl-methyl]-pyrrolidine-3R-carboxylic acid) in mouse whole blood was developed, validated and utilized in GLP toxicokinetic evaluations. Six 40-µl whole blood samples were collected from a single mouse over the course of a 12 h blood collection window. To avoid sample volume losses, whole blood was selected as the matrix in place of the more typically used plasma. A 10-µl assay volume was used to ensure sufficient volumes are available for dilutions, repeats and incurred sample reanalysis. The samples (10-µl aliquot) were fortified with stable-labeled internal standard (d18-atrasentan) and lysed thoroughly prior to protein precipitation. The chromatographic separation was performed on a Zorbax(®) SB-C18 (50 x 2.1 mm; 5 µm) HPLC column with a mobile phase consisting of 25 mM ammonium acetate and 0.25% (v/v) acetic acid in 50/50 (v/v) acetonitrile/water. The MS measurement was conducted under positive ion mode using multiple-reaction monitoring of m/z 511→354 for analyte and 529→354 for stable-labeled internal standard. The peak area ratio (analyte:stable-labeled internal standard) was used to quantitate atrasentan. RESULTS: A dynamic range of 5-1400 ng/ml was established after validation. The challenges associated with a small-volume whole-blood assay involved anticoagulant overloading with commercial blood collection tubes, managing phospholipids to ensure a robust assay and automation. In-depth discussions are provided in this article. The validated method was then used for GLP toxicokinetic evaluations. To demonstrate the method reproducibility, approximately 10% of the incurred samples from the study were repeated in singlet. Excellent assay reproducibility was demonstrated where 100% of samples met incurred sample reanalysis acceptance criteria. CONCLUSION: Good quality exposure data were obtained from every serial sampled mouse in the study.

Vernakalant hydrochloride: A novel atrial-selective agent for the cardioversion of recent-onset atrial fibrillation in the emergency department.

OBJECTIVES: Vernakalant is a relatively atrial-selective antiarrhythmic agent that has been shown to successfully convert atrial fibrillation (AF) to normal sinus rhythm for some patients whose onset of dysrhythmia occurred less than 7 days previously. This study sought to evaluate the efficacy and safety of vernakalant for patients with recent-onset AF. METHODS: This was a post hoc analysis of patients with recent-onset AF (> 3 to ≤ 48 hours) enrolled in the double-blind, placebo-controlled Atrial arrhythmia Conversion Trial (ACT) I and the open-label ACT IV trials. The studies enrolled adults presenting with AF to 78 emergency departments (ED) and cardiac clinics in six countries. Patients received a 10-minute intravenous infusion of vernakalant or placebo, followed by an additional infusion if necessary. Efficacy assessments included conversion to sinus rhythm within 90 minutes and median time to conversion. Safety evaluations included telemetry, Holter monitoring, and adverse events (AEs). RESULTS: Of the 290 patients, 229 received vernakalant, 61 received placebo, and the overall mean age was 59 years. The vernakalant and placebo groups were similar. Of all patients given vernakalant, 136 (59.4%) converted to sinus rhythm within 90 minutes, compared with three (4.9%) placebo patients. The median time to conversion with vernakalant was 12 minutes (interquartile range = 7-24.5 minutes). Clinically significant bradycardia and hypotension were uncommon, and no cases of torsade de pointes or ventricular fibrillation occurred. CONCLUSIONS: Vernakalant rapidly converted recent-onset AF to sinus rhythm in over half of patients, was well tolerated, and has the potential to offer an important therapeutic option for rhythm control of recent-onset AF in the ED.