Identification of unknown impurities in simvastatin substance and tablets by liquid chromatography/tandem mass spectrometry

Unknown impurities were detected in simvastatin substance and tablets at a 0.2% level using the liquid chromatography technique with UV (DAD) detection. The impurity structures were elucidated by a direct hyphenation of liquid chromatograph to high-resolution mass spectrometer with electrospray ionisation interface using solutions of formic acid in water and in acetonitrile as the mobile phase. Peak tracking was performed using the column-switching technique. Accurate mass measurements by quadrupole time-of-flight mass spectrometer equipped with lock-spray provided information about elemental composition of intact molecules and fragments of impurities. Measurement accuracy for precursor ions was around 3 ppm and for fragment ions between 4 and 13 ppm. Mass resolving power was around 6500. Deduced molecular formulae for A1, A2 and A3 impurities were C(27)H(44)O(6), C(26)H(43)O(6) and C(26)H(41)O(5), respectively. The structures proposed for all three impurities revealed modifications of simvastatin molecule on the lactone ring. Impurity A1, detected in simvastatin tablets, was identified as ethyl ester, while the impurities A2 and A3, detected in simvastatin substance, were identified as methyl ester and methyl ether of simvastatin. The impurity from tablets was synthesized and its structure confirmed by LC-UV, LC-MS/MS, and NMR techniques.     

Speciation and separation of Cr(VI) and Cr(III) using coprecipitation with Ni/2-Nitroso-1-naphthol-4-sulfonic acid and determination by FAAS in water and food samples

A speciation procedure for chromium(III) and chromium(VI) in the water and food samples has been established in the presented work. The procedure presented based on quantitative recoveries of Cr(III) > 95% using coprecipitation of Ni²⁺/2-Nitroso-1-naphthol-4-sulfonic acid. The total chromium was measured after reduction of Cr(VI) by concentrated H₂SO₄ and ethanol. The Cr(VI) was calculated as the difference between the total Cr content and the Cr(III) contents. The analytical variables, pH, amounts of precipitate, sample volume for optimum recoveries of Cr(III) were investigated. The influences of the some alkaline and earth alkaline ions and some transition metals on the recoveries of analyte ions were also investigated. The preconcentration factor was 50. The detection limit (3σ) of the reagent blank for chromium(III) was 1.33 μg L⁻¹. The relative standard deviations for determinations were found to be <7%, and % of relative error was calculated <6%. The method was validated by certified reference materials of tea (GBW 07605) and bush branches and leaves (GBW 0703). The procedure was successfully applied to the speciation of chromium in natural water and food samples (fish, white cheese, cow’s meat, black tea, boiled wheat).     

Effect of EDTA,Sodium Hypochlorite,and Chlorhexidine Gluconate with or without Surface Modifiers on Dentin Microhardness

Introduction

This study aimed to evaluate the effects of root canal irrigants on the microhardness of root canal dentin in the presence and absence of surface-modifying agents.

Methods

Forty-eight root halves were prepared by longitudinal splitting of the distal roots of 24 freshly extracted mandibular human third molars and embedded in autopolymerizing acrylic resin, leaving the dentin surface exposed. After polishing, the microhardness values of the untreated dentin surfaces were recorded by using Vickers tester at the mid-root level. The root halves were randomly assigned to 6 groups composed of 8 samples each and treated for 5 minutes with one of the following irrigants: 17% EDTA, REDTA, 2% chlorhexidine gluconate (CHX), 2% CHX with surface modifiers (CHX-Plus), 6% NaOCl, or 6% NaOCl with surface modifiers (Chlor-XTRA). After surface treatment, dentin microhardness values were recorded at close proximity to the initial indentation areas. Experimental data were statistically analyzed by using the t test and one-way analysis of variance, followed by Tukey honestly significant difference test at α = 0.05.

Results

EDTA, REDTA, NaOCl, and Chlor-XTRA significantly decreased the microhardness of root dentin compared with intact controls (P < .05).

Conclusions

The addition of surface modifiers to the irrigants did not affect the microhardness of the samples.     

Quality of life in Turkish patients with Familial Mediterranean Fever: Association with fatigue,psychological status,disease severity and other clinical parameters

Aim of the work: To evaluate the quality of life (QoL) in Familial Mediterranean Fever (FMF) patients, and determine its association with fatigue, depression, disease severity and other clinical parameters. Patients and methods: Sixty FMF patients were included. QoL was assessed by Short Form-36 (SF-36), depression by Hamilton Depression Scale (HDS), and fatigue by Fatigue severity scale (FSS). Disease severity score and Mutations of the Mediterranean fever (MEFV) gene were assessed. Results: The mean age of patients was 33.73 ± 9.81 years and disease duration 14.6 ± 12.1 years. They were 35 females and 25 males. FMF patients scored significantly higher in FSS (29.9 ± 17.6) and HDS (15.1 ± 8.5) compared to the control (10.6 ± 7.1 and 6.3 ± 9.4; p < 0.0001 respectively) while all SF36 sub-items except mental health were significantly lower (p < 0.05). MEFV gene mutation was present in 49 (81.7%) patients. The visual analogue scale of pain significantly negatively correlated with the FSS (p < 0.0001), HDS (p < 0.0001) and all SF36 sub-items except mental health (p < 0.0001). Disease duration, age of onset, and duration of attacks showed no significant correlation with FSS, HDS and SF36. Delay in diagnosis significantly correlated with FSS (p < 0.0001) and negatively with SF36 sub-items physical role (p = 0.02), general health (p = 0.01) and social functioning (p = 0.03). Age of diagnosis significantly correlated with FSS (p = 0.03) and negatively with SF36-vitality (p = 0.047). There was a significant effect of disease severity on QoL, fatigue and depression (p < 0.05). Conclusion: QoL is associated with fatigue, depression and disease severity in FMF patients. It should be used in routine clinical evaluation as an outcome measure in FMF.     

Effects of Single-Dose Preemptive Pregabalin and Intravenous Ibuprofen on Postoperative Opioid Consumption and Acute Pain after Laparoscopic Cholecystectomy

Purpose: Non-opioid medications as a part of multimodal analgesia has been increasingly suggested in the management of acute post-surgical pain. The present study was planned to compare the efficacy of the combination of pregabalin plus ?v ibuprofen. Methods: 58 patients were included in this prospective, randomized, double-blinded study. The pregabalin group (Group P, n = 29) received 150 mg pregabalin, the pregabalin plus ibuprofen group (Gropu PI, n = 29) received 150 mg pregabalin and 400mg ?v ibuprofen before surgery. Postoperative fentanyl consumption, additional analgesia requirements and PACU stay were recorded. Postoperative analgesia was performed with patient-controlled IV fentanyl. Results: VAS scores in the group PI were statistically lower at PACU, 1and 2 hours at rest, at PACU, 1, 2, 4, 12 and 24 hours on movement compared to the group P (P < 0.05). Opioid consumption was statistically significantly higher in the group P compared to the group PI (130.17 ± 60.27 vs 78.45 ± 60.40 μq, respectively, P < 0.001) and reduced in the 4th 24 hours by 55% in group PI. Rescue analgesia usage was statistically significantly higher in the group P than in the group PI (16/29 vs 7/29, respectively, P < 0.001). Four patient in the group PI did not need any opioid drug. Besides, PACU stay was shorter in the group PI than the group P (10.62 ± 2.38 vs 15.59 ± 2.11 min, respectively, P < 0.001). Conclusion: Preemptive pregabalin plus ?v ibuprofen in laparoscopic cholecystectomy reduced postoperative opioid consumption. This multimodal analgesic aproach generated lower pain scores in the postoperative period.     

Immunoglobulin specificity of low grade B cell gastrointestinal lymphoma of mucosa-associated lymphoid tissue (MALT) type.

The specificity of the tumor cell immunoglobulin in three cases of low grade B cell gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma has been studied. Using anti-idiotypic antibodies to detect the reactivity of tumor immunoglobulin in tissue sections from the patients and other individuals, we observed specificity for normal tissue components in all three cases studied. Reactivity in one case was with follicular dendritic cells, in the second case with a novel antigen on mucosal post capillary venules, and, in the third case, a broad pattern of reactivity was observed. This study suggests that autoimmunity may play a role in the pathogenesis of gastric lymphoma.     

Spontaneous external jugular vein pseudoaneurysm treated by thrombin injection: Case report and literature review

Although external jugular vein (EJV) aneurysms are infrequent, regardless of etiology, spontaneous pseudoaneurysms (PAs) are extremely rare and generally require surgery. We describe a case of spontaneous PA of the EJV, which was successfully treated by percutaneous thrombin injection.