抗癌药物不良反应的职业防护

作者简要介绍了抗癌药物对制药人员和医务人员健康的危害，以及如何对暴露于该类药物的人群进行监测的方法。目前国外研究认为，防护的最佳途径是加强操作中的保护措施和对有关人员进行相关知识的教育。     

辖区内职业健康情况分析及职业健康监护模式的探讨

目的对辖区内职业危害接触员工职业健康情况进行分析及职业健康模式进行探讨。方法选取2010年1月至2012年11月我辖区内不同职业危害接触员工24731例,其中,16678例为男性,8053例为女性,年龄为22~60岁,平均年龄为(43.3±6.9)岁。对上述员工的职业健康情况进行了相关分析,并对其职业卫生健康模式进行了探讨。结果辖区内以接触化学毒物人数最多,其中男性职工中,患职业病及疑似职业病者为637例,占比3.8%,女性患病者为123例,占比1.5%。患病情况和性别没有显著关系(P>0.05)。辖区内2010年至2012年职业病(包括疑似职业病)分类其中职业性中毒、尘肺病最为常见,其次是职业性噪声聋,职业性放射病比较少见。结论构建完善职业健康监护模式能有效提升职工的健康水平,应受到高度的重视。     

艾滋病患者职业暴露与防护的护理管理

目的：对艾滋病患者职业暴露和防护管理进行探讨。方法：选择2005年11月～2009年12月收治的艾滋病患者15例,提出了即时的防范对策,不断加强医务人员的全面防护的相关教育及培训,预防传染的发生,以减少医务人员HIV职业暴露的发生。结果：15例患者中13例病灶好转后转院,1例死亡,1例因放弃治疗而终止,在护理过程中医务人员没有发生任何传染,防护率达到100%,取得了很好的效果。结论：HIV的职业暴露影响重大,应提高认识,加强管理,才能预防传染的发生。     

Occupational exposure to nanomaterials: Present knowledge and future development

Although unintentional exposure to nanoparticles (NP) is not new in an occupational setting, the global production for specially-engineered nanomaterials (NM) is expected to grow in the next few years, thus requiring an additional recruitment of workers across the world. Among the possible exposure scenarios, the workplaces where NM are produced, processed, used and disposed, may pose specific challenges. Field surveys have shown that workers from nanotechnology industries and R&D facilities have the potential to be exposed by inhalation to aerosols of NM, and skin contamination is not negligible. Owing to the lack of a robust body of scientific evidence on NM hazards, along with the inadequate knowledge on the dose-response relationships as well as long-term consequences to health, only a qualitative risk assessment of a few class of NM is possible. Exposure assessment in new NP processes has begun under the uncertainty about metrology and the lack of internationally recognized occupational standards and exposure limits, but in the near future improvements are expected. Given the limited amount of information about the health risks associated with occupational exposure to engineered NP, the precautionary principle suggests to take measures to minimize worker exposures. Implementing appropriate engineering controls, using personal protective equipment, establishing safe handling procedures, together to monitor worker's health, are all strategic elements of a risk management programme at workplace.     

职业健康监护在职业病防治中的作用探讨

目的为广大企业尤其是中小企业职业卫生工作进行合理有效的监督管理和服务提供线索。方法通过对日常职业卫生监督工作中遇见的2个具体案例进行分析。结果2个案例中，1个通过开展职业健康监护，及时发现了14名员工白细胞异常，避免了一起群体性苯中毒事故的发生；另外1个由于没有开展上岗前职业健康检查，从而导致职业性轻度噪声聋的发生。结论职业健康监护能有效的防止职业病的发生。     

Liquid chromatography tandem mass spectrometry assay to determine the pharmacokinetics of aildenafil in human plasma

A simple, sensitive and specific liquid chromatography/tandem mass spectrometry method for the quantitation of aildenafil, a new phosphodiesterase V inhibitor, in human plasma is presented. The analyte and internal standard, sildenafil, were extracted by a one-step liquid-liquid extraction in alkaline conditions and separated on a C(18) column using ammonia:10mM ammonium acetate buffer:methanol (0.1:15:85, v/v/v) as the mobile phase. The detection by an API 4000 triple quadrupole mass spectrometer in multiple-reaction monitoring mode was completed within 2.5 min. The calibration curve exhibited a linear dynamic range of 0.05-100 ng/ml with a 10 pg/ml limit of detection. The intra- and inter-day precisions measured as relative standard deviation were within 8.04% and 5.72%, respectively. This method has been used in a pharmacokinetic study of aildenafil in healthy male volunteers each given an oral administration of one of the three dosages.     

Occupational exposure to antineoplastic agents induces a high level of chromosome damage. Lack of an effect of GST polymorphisms

The aim of our study was to investigate whether occupational exposure to antineoplastic drugs (AND) resulted in genetic damage, possibly indicative of adverse health effects in the long term. We performed a chromosomal aberrations (CA) analysis in peripheral blood lymphocytes (PBL) of a group of 76 trained nurses occupationally exposed to AND. Furthermore, we analysed whether genetic polymorphisms in four metabolic genes of the glutathione S-transferase (GST) family involved in antineoplastic drugs detoxification (GSTM1, GSTT1, GSTP1, GSTA1) had any effect on the yield of chromosomal aberrations in nurses exposed to antineoplastic agents. The exposed group showed a very significant increase of genetic damage (p<0.0001) potentially indicative of an increased risk of cancer. Unexpectedly, besides the elevated level of chromatid-type aberrations usually related to exposure to chemical agents, we found also severe chromosome damages such as chromosome deletions and dicentric chromosomes, usually related to radiation exposure. No significant association was detected between all GSTs genotypes and chromosome damage. In conclusion, our data show how the occupational exposure to AND is associated to a potential cancer risk, suggesting that current prevention methods do not completely eliminate opportunities for exposure and supporting the need to improve the actual safety practices.     

Liquid chromatography tandem mass spectrometry method for simultaneous determination of antidiabetic drugs metformin and glyburide in human plasma

A simple and rapid liquid chromatography/tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous quantitation of antidiabetic drugs metformin and glyburide in human plasma using glimepiride as internal standard (IS). After acidic acetonitrile-induced protein precipitation of the plasma samples, metformin, glyburide and IS were chromatographed on reverse phase C18 (50 mm x 4.6 mm i.d., 5 microm) analytical column. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 3.5 min and calibration curves were linear over the concentration range of 20-2500 ng/ml for metformin and 5-500 ng/ml for glyburide. The method was validated for selectivity, sensitivity, recovery, linearity, accuracy and precision, dilution integrity and stability studies. The recoveries obtained for the analytes and IS (>or=69%) were consistent and reproducible. Inter-batch and intra-batch coefficient of variation across four validation runs (LLOQ, LQC, MQC and HQC) was less than 8%. The accuracy determined at these levels was within +/-8% in terms of relative error (RE). The method was applied to a bioequivalence study of 500 mg metformin and 5mg of glyburide tablet after oral administration to 28 healthy human subjects under condition of fasting.     

降糖保健食品中非法添加盐酸苯乙双胍和格列本脲的检测

目的:建立检测降糖保健食品中非法添加化学成分盐酸苯乙双胍和格列本脲的定性、定量检测方法.方法:采用薄层色谱法、高效液相色谱-二极管阵列检测法、LC/MS/MS联用技术进行定性鉴别,并采用高效液相色谱法测定其中盐酸苯乙双胍和格列本脲的含量.结果:在抽取的9种市售样品中,有3种检出了盐酸苯乙双胍和格列本脲,1#～3#阳性样品中添加的盐酸苯乙双胍和格列本脲分别为8.54、6.51、10.53 mg/g和6.01、4.04、2.70 mg/g.结论:该方法快速、准确、灵敏、可靠,可用于有效监测保健食品中非法添加的盐酸苯乙双胍和格列本脲.     

Simultaneous determination of amoxicillin and ambroxol in human plasma by LC-MS/MS: validation and application to pharmacokinetic study

A rapid, simple and sensitive LC-MS/MS method was developed for simultaneous determination of amoxicillin and ambroxol in human plasma using clenbuterol as internal standard (IS). The plasma samples were subjected to a simple protein precipitation with methanol. Separation was achieved on a Lichrospher C(18) column (150 mm x 4.6mm ID, dp 5 microm) using methanol (containing 0.2% of formic acid) and water (containing 0.2% of formic acid) as a mobile phase by gradient elution at a flow rate of 1.0 mL/min. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring (MRM) mode by monitoring the ion transitions from m/z 365.9-->348.9 (amoxicillin), m/z 378.9-->263.6 (ambroxol) and m/z 277.0-->203.0 (IS). Calibration curves were linear in the concentration range of 5-20,000 ng/mL for amoxicillin, and 1-200 ng/mL for ambroxol, with the intra- and inter-run precisions of <9% and the accuracies of 100+/-7%. The method has been validated and applied to pharmacokinetic studies of compound amoxicillin and ambroxol hydrochloride tablets in healthy Chinese volunteers.     

Simultaneous determination of ciclesonide and its active metabolite desisobutyryl-ciclesonide in human plasma by LC-APCI-MS/MS: application to pharmacokinetic study in healthy Chinese volunteers

A sensitive and highly selective liquid chromatography tandem mass spectrometric (LC/MS/MS) method was developed and validated for the determination of ciclesonide (CIC) and its active metabolite, desisobutyryl-ciclesonide (des-CIC), in human plasma. Plasma samples were extracted using methyl tert-butyl ether with mifepristone as an internal standard (IS). Separation was carried out on a C(18) column using a mixture of 0.1% formic acid solution and methanol as the mobile phase with linear gradient elution. The detection was operated with positive atmospheric pressure chemical ionization (APCI) by selective multiple reaction monitoring (SRM). The chief benefit of the present method was the high sensitivity, with the lower limit of quantification (LLOQ) as low as 10pg/mL and the linearity ranging from 10 to 10,000pg/mL for both CIC and des-CIC. The method was fully validated and successfully applied to determine CIC and des-CIC simultaneously in human plasma and proved to be suitable for phase I clinical pharmacokinetic study of inhaled ciclesonide in healthy Chinese volunteers.     

Quantitative assay for bradykinin in rat plasma by liquid chromatography coupled to tandem mass spectrometry

An assay to quantify bradykinin in rat plasma has been developed and validated, using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Sar-D-Phe(8)-des-Arg(9)-bradykinin was used as internal standard. Aprotinin was added to rat plasma to inhibit the activity of proteinases. Recoveries for solid-phase extraction (SPE) on Strata X reversed phase were greater than 80%. Multiple reaction monitoring (MRM) on a triple quadrupole mass spectrometer equipped with an electrospray source (ESI), operating in the positive ion-mode, was used for detection. The assay was validated and stability was explored. Bradykinin (10-500 ng/mL) was quantified with accuracy values (% RE) below 10% and intra- and inter-day precisions (% RSD) below 12 and 16%, respectively, for all concentrations. The method was successfully applied to several plasma samples from low levels kallikrein rats (LKRs) compared with normal kallikrein rats (NKRs).     

UPLC-MS/MS法快速检测减肥类保健食品中7种违法添加的药物

目的 建立专属、灵敏的UPLC-MS/MS方法快速检测保健食品中7种违法添加的药物.方法 样品经甲醇提取后,采用超高效液相色谱/电喷雾离子化质谱法测定.色谱条件:Agilent EC-C18(150 mm×2.1 mm×2.7 μm),柱温30℃,以甲醇-0.1％乙酸铵溶液为流动相进行梯度洗脱,流速0.3 mL·min-1;质谱条件:以电喷雾电离源,正、负离子模式进行质谱数据采集,选择正负离子全扫描、多反应监测(MRM)方式检测7种违法添加减肥药物.通过比较样品峰与对照品峰的保留时间、相对分子质量和二级质谱碎片信息,确定样品中是否违法添加了化学药物.结果 在上述色谱及质谱条件下,7种违法添加药物的色谱图分离度良好,质谱分辨率符合鉴别要求.UPLC-MS/MS方法测定上述化学物质的最小检出量为0.03～1.00 ng.结论 该方法专属性强、灵敏度高,快捷,可作为N,N-西布曲明等7种违法添加药物的有效检测方法.     

2009-2011年宁夏部分企业有毒有害作业工人职业健康监护分析

目的分析宁夏部分有毒有害作业工人职业健康监护现状,为宁夏回族自治区职业病防治决策提供依据。方法对宁夏部分企业有毒有害作业工人职业健康监护情况进行描述性研究,分析不同企业规模、经济类型、行业性质及接触不同有害因素作业工人的健康监护情况,并分析2009～2011年职业健康监护变化趋势。结果2009～2011年宁夏各种有毒有害作业工人职业健康体检受检率呈总体上升趋势。疑似职业病栓出率大型企业最高,小型企业最低;国有企业最高,集体和外资企业最低。煤炭行业、粉尘作业工人疑似职业病检出率最高,粉尘是主要危害因素。结论应进一步加强职业病宣传、监督及人才队伍建设,提高健康监护工作水平。     

Simultaneous determination of a p38 MAP kinase inhibitor and its amide hydrolyzed metabolite in Cynomolgus monkey plasma by LC-MS/MS, and its application to a toxicokinetic study

A LC-MS/MS method was developed for the determination of a p38 MAP kinase inhibitor (Compound I) and its amide hydrolyzed metabolite (M7) in Cynomolgus monkey plasma over the concentration range of 1.00-1000ng/mL. Stable isotope labeled compounds (d(3)-Compound I and d(3)-M7) were used as internal standards (IS). Samples were prepared using protein precipitation in the 96-well format with a 30μL plasma sample volume. Chromatographic separation was performed with reversed-phase liquid chromatography on a Varian Monochrom C(18) (100mm×2.00mm, 5μm) analytical column. The mobile phases were 5mM ammonium formate in acetonitrile/water (95/5, v/v) pH 7.0 and 5mM ammonium formate in acetonitrile/water (5/95, v/v) pH 7.0. Gradient elution, at a flow rate of 550μL/min, was used to separate Compound I and M7. Positive atmospheric pressure chemical ionization was utilized with detection by multiple reaction monitoring (MRM). Total run time was about 3.2min. This method was validated following the current Food and Drug Administration (FDA) guidance for bioanalytical method validation. The intra- and inter-day precision (% CV) and accuracy (% bias) at all concentrations tested were below 15% for both analytes. The mean recoveries for Compound I, M7, d(3)-Compound I, and d(3)-M7 were 106%, 107%, 108% and 105%, respectively. The method was successfully applied to support a GLP toxicokinetic study in Cynomolgus monkeys after oral administration of Compound I. A total of 48 samples (～12.5% of the total number of samples) were selected for incurred sample reanalysis (ISR). The % difference between the reassay concentrations and the original concentrations were all less than 20% of their mean values and met the acceptance criteria for ISR.     

Determination of chamaechromone in rat plasma by liquid chromatography-tandem mass spectrometry: application to pharmacokinetic study

A rapid, simple and accurate method was developed for the determination of chamaechromone in rat plasma using liquid chromatography tandem mass spectrometry (LC–MS–MS). Rosuvastatin was used as the internal standard. The plasma samples were extracted by liquid–liquid extraction with ethyl acetate. Chromatographic separation was performed on Xbridge™ C₁₈ column (2.1 mm × 50 mm, 3.5 μm) with linear gradient elution using water and methanol, both of which were acidified with 0.1% aqueous formic acid. The flow rate was 0.4 mL/min and the total run time was 6 min. Detection was performed on a triple-quadrupole tandem mass spectrometer using positive ion mode electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. The MS/MS ion transitions monitored were m/z 543.3 → 198.9 and 481.9 → 258.3 for chamaechromone and rosuvastatin, respectively. Good linearity was observed over the concentration range of 8–6400 ng/mL in 0.1 mL of rat plasma. The lowest concentration (8 ng/mL) in the calibration curve was estimated as LLOQ with both deviation of accuracy and RSD of precision <20% (n = 6). Intra-assay and inter-assay variability were less than 11% in plasma. This method was successfully applied to a pharmacokinetic study of chamaechromone in rats after intravenous (5 mg/kg) and oral (100 mg/kg) administration. Following oral administration the concentration–time curve of chamaechromone exhibited a biphasic absorption profile. The maximum mean concentration in plasma (C_max, 795.9 ± 14.6 ng/L) was achieved at 11.3 ± 0.8 h (T_max) and the area under curve (AUC_0–60) was 6976.7 ± 1026.9 ng h/L. After single intravenously administration of chamaechromone, the essential pharmacokinetic parameters C_max, AUC_0–48 were 4300.7 ± 113.6 ng/L and 3672.1 ± 225.4 ng h/L, respectively. The result showed that the compound was poorly absorbed with an absolute bioavailability being approximately 8.9%.     

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of tenofovir and emtricitabine in human plasma and its application to a bioequivalence study

A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for simultaneous quantification of Tenofovir (TEN) and Emtricitabine (EMT) in human plasma using Chromolith Speed Rod RP18. The mass transition ion-pair has been followed as m/z 288.10-->176.10 for TEN, m/z 248.20-->130.20 for EMT and m/z 230.10-->112.10 for Lamivudine (LAM). The method involves solid phase extraction from plasma, simple isocratic chromatographic conditions and mass spectrometric detection using an API 5000 instrument that enables detection at nanogram levels. Lamivudine was used as the internal standard. The proposed method has been validated with a linear range of 10-600 ng/ml for TEN and 25-2,500 ng/ml for EMT. The intrarun and interrun precision values are within 12.0% for TEN and 15.6% for EMT at their respective LOQ levels. The overall recoveries for TEN and EMT were 84.3% and 68.5%, respectively. Total elution time was as low as 2 min.     

两种妈咪宝保健帖中药基质挥发油成分的GC/MS分析

目的对比研究A、C两种妈咪宝保健帖中药基质挥发油成分及含量.方法水蒸气蒸馏法提取挥发油,GC/MS/DS联用方法检测结果.结果A、C两种妈咪宝保健帖中药基质挥发油含有10种相同成分,其中三甲基肼、桂醛、夹竹桃麻素三种成分的百分含量较高.结论挥发油主成分中的桂醛、夹竹桃麻素是A、C妈咪宝保健帖的有效成分.     

佛山市公安干警艾滋病职业暴露防护相关知识调查

目的了解佛山市公安干警对艾滋病职业暴露相关知识的知晓率情况,为开展对警察艾滋病健康教育知识与技能培训提供资料。方法采用自行设计问卷,对参加警察学校培训255名公安干警学员就艾滋病职业暴露相关知识进行问卷调查。结果①公安干警对艾滋病知识知晓率较高,达到86.65%;②艾滋病"窗口期"概念知晓率较低,仅为42.75%;③艾滋病职业暴露后,保密工作及伤口处理方式认知不足,仅52.94%人认为要做好保密工作,53.33%的调查对象错误的认为发生职业暴露后要局部按压伤口。结论佛山市公安干警对艾滋病知识知晓率较高,但部分艾滋病职业暴露防护知识知晓率较低,应对公安干警应有针对性的开展艾滋病知识培训,培训重点需要放在公安干警知晓率较低的相关知识上,提高他们对艾滋病防护意识和自我保护能力