Objective To develop a matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) approach to identify Staphylococcus aureus (S. aureus) and differentiate methicillin-resistant S. aureus (MRSA) from methicillin-sensitive S. aureus (MSSA). Methods A total of 100 S. aureus strains isolated from clinical specimens and farm workers were collected and analyzed by MALDI-TOF-MS. And data obtained were interpreted with biotyper software. Results Ninety-two strains were identified by MALDI-TOF-MS as S. aureus at a level of secure genus and probable species, and 4 strains were identified at probable genus after their cultivation, spectral collection and data preprocessing. One strain was identified as S. aureus with lower score. It was revealed that identification of S. aureus by MALDI-TOF-MS was highly correlated with typing by biochemical and serological methods with an accuracy as high as 97%. The biotyper cluster analysis showed that 100 isolates were divided into 2 types at the distance level of 400. Higher peak intensity in the mass of both 3784 Da and 5700 Da was observed in MRSA, whereas that was absent from MSSA. Conclusion MALDI-TOF-MS is considered as a simple, rapid and highly reproducible technique with high-throughput and accuracy for the identification of S. aureus and it can reliably differentiate MRSA from MSSA.

杭州地区1998-2008年产ESBL的志贺菌基因型及分子流行病学研究

1999年Ahamed和Kundu~([1])在印度首次发现了志贺菌中存在SHV-11型ESBL.ESBL通常由质粒介导,对三代头孢和单环类抗生素有很高的活性,此后,世界各地均有志贺菌中ESBL的报道.

心脏核磁共振成像技术在肥厚型心肌病中的应用现状及新进展

肥厚型心肌病是一种为常见的遗传性心肌病,患病率约为1/500,是导致青年猝死的首要病因,也是引起不同年龄段心力衰竭与脑卒中的主要病因之一~([1-8]).肥厚型心肌病-是一种常染色体显性遗传病,现已明确至少12个编码肌小节蛋白的基因突变,导致心室肥厚的表型~([2-3,6]).

用于冠心病的超声诊断新技术进展

目前,在冠心病患者超声波诊断领域内新技术的发展比较快,主要包括室壁的声学定量与彩色动力分析、谐波显像技术、多普勒组织成像技术(如多普勒组织速度图、多普勒组织加速度图、多普勒组织能量图)、心肌组织定征学(tissue characterization)等.

风险评估在化工行业职业危害评价中的应用

危险性评价和管理理论始于1983年,由美国国家研究委员会(NRC)首先提出,并将其划分为危害识别(Hazard identification)、剂量-反应评价(Dose response assessment)、暴露评价(Exposure assessment)和危险度描述(Risk characterization)4个阶段[1].自此,围绕危险性评价与管理的4个阶段对环境污染物致机体危害的危险性评价技术和方法得到了广泛应用[2-3].危险度评价与管理模式是由多步骤组成的,关于识别、分析和评价职业危害,确定危险度水平和管理危险度的一个系统的关联过程.

Anesthetic-Induced Developmental Neurotoxicity

1 IntroductionMillions of newborn and infants receive anesthetic,sedative and analgesic drugs for surgery and painful procedures on a daily basis.Recent laboratory reports clearly demonstrate that anesthetic and sedative drugs induced both neuroapoptosis and neurocognitive deficits in laboratory models.This issue is of paramount interest to pediatric anesthesiologists and intensivists because it questions the safety of anesthetics used for fetal and neonatal anesthesia[1-2].In an attempt to summarize the rapidly expanding laboratorybased literature on anesthetic-induced developmental neurotoxicity (AIDN),this review will examine published reports on the characterization,mechanisms and alleviation of this phenomenon.

In the present study, comprehensive stress testing of amlodipine (AM) was carried out according to International Conference on Harmonization (ICH) Q1A(R2) guideline. AM was subjected to acidic, neutral and alkaline hydrolysis, oxidation, photolysis and thermal stress conditions. The drug showed instability in acidic and alkaline conditions, while it remained stable to neutral, oxidative, light and thermal stress. A total of nine degradation products (DPs) were formed from AM, which could be separated by the developed gradient LC method on a C18 column. The products formed under various stress conditions were investigated by LC–MS/MS analysis. The previously developed LC method was suitably modified for LC–MS/MS studies by replacing phosphate buffer with ammonium acetate buffer of the same concentration (pH 5.0). A complete fragmentation pathway of the drug was first established to characterize all the degradation products using LC–MS/MS and multi-stage mass (MSn) fragmentation studies. The obtained mass values were used to study elemental compositions, and the total information helped with the identification of DPs, along with its degradation pathway.

A simple, precise, accurate stability-indicating gradient reversed-phase high-performance liquid chromatographic (RP-HPLC) method was developed for the quantitative determination of zotepine (ZTP) in bulk and pharmaceutical dosage forms in the presence of its degradation products (DPs). The method was developed using Phenomenex C18 column (250 mm ~ 4.6 mm i.d., 5 mm) with a mobile phase containing a gradient mixture of solvents, A (0.05%trifluoroacetic acid (TFA), pH ? 3.0) and B (acetonitrile). The eluted compounds were monitored at 254 nm;the run time was within 20.0 min, in which ZTP and its DPs were well separated, with a resolution of 41.5. The stress testing of ZTP was carried out under acidic, alkaline, neutral hydrolysis, oxidative, photolytic and thermal stress conditions. ZTP was found to degrade significantly in acidic, photolytic, thermal and oxidative stress conditions and remain stable in basic and neutral conditions. The developed method was validated with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness as per ICH guidelines. This method was also suitable for the assay determination of ZTP in pharmaceutical dosage forms. The DPs were characterized by LC-MS/MS and their fragmentation pathways were proposed.

A new impurity was detected during high performance liquid chromatographic (HPLC) analysis of eslicarbazepine acetate active pharmaceutical ingredient. The structure of unknown impurity was postulated based on liquid chromatography mass spectrometry using electrospray ionization and ion trap analyzer (LC/ESI-IT/MS) analysis. Proposed structure of impurity was unambiguously confirmed by synthesis followed by characterization using 1H, 13C nuclear magnetic resonance spectrometry (NMR), 1H-1H correlation spectro-scopy (COSY) and infrared spectroscopy (IR). Based on the spectroscopic and spectrometric data, unknown impurity was characterized as 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl propionate.

Leflunomide (LLM) is subjected to forced degradation under conditions of hydrolysis, oxidation, dry heat, and photolysis as recommended by International Conference on Harmonization guideline Q1A(R2). In total, four degradation products (I–IV) were formed under different conditions. Products I, II and IV were formed in alkaline hydrolytic, acidic hydrolytic and alkaline photolytic conditions. LLM and all degradation products were optimally resolved by gradient elution over a C18 column. The major degradation product (IV) formed in hydrolytic alkaline conditions was isolated through column chromatography. Based on its 1H NMR, IR and mass spectral data, it was characterized as a British Pharmacopoeial impurity B. The HPLC method was found to be linear, accurate, precise, sensitive, specific, rugged and robust for quantification of LLM as well as product IV. Finally, the method was applied to stability testing of the commercially available LLM tablets.