静脉药物调配中心集中调配人员抗肿瘤药物职业暴露的评估

发布时间：2018-06-10 03:38

本文选题：抗肿瘤药物 + 职业暴露　；参考：《苏州大学》2013年硕士论文

【摘要】：目的：通过对静脉药物调配中心（PIVAS）抗肿瘤药物配置区域进行环境监测与生物监测，评估集中调配人员在工作环境中抗肿瘤药物的暴露情况，旨在为政府部门和医疗机构对抗肿瘤药物配置的管理提供依据。方法：（1）选择某三甲医院PIVAS中30名接触抗肿瘤药物配置的药学人员为暴露组，30名不接触抗肿瘤药物配置的健康人员作为控制组，通过问卷调查收集人员的年龄、性别、饮食、吸烟情况、工作岗位、工作年限、防护措施等基本信息。（2）环境检测：选择环磷酰胺、阿糖胞苷为环境监测的生物标记物，用超高效液相串联质谱法（UPLC-MS/MS）测定医院PIVAS不同的环境擦拭样本和调配人员手套和口罩内侧及外侧的抗肿瘤药物的残留浓度。（3）生物监测：用UPLC-MS/MS测定尿液环磷酰胺的浓度；采用Annexin-V-PI双染色后，流式细胞仪检测淋巴细胞凋亡率；酶联免疫吸附测定（Elisa）法测定尿液8-OHdG/Cr值；利用鼠伤寒杆菌TA98和TA100分别对尿浓缩液进行致突变的微量波动试验。结果：（1）分别对调查对象的基本资料进行分析比较，暴露组和控制组在年龄、性别、饮食、吸烟情况均无统计学差异，，基线均衡，具有可比性。（2）建立了UPLC-MS/MS测定擦拭样本中环磷酰胺和阿糖胞苷浓度的方法，并进行了方法学确证。PIVAS中生物安全柜、地面、药架、药箱、电话、冰箱把手、传递仓门把手均存在不同程度的环磷酰胺和阿糖胞苷污染。污染最严重的是生物安全柜操作台面，阿糖胞苷平均污染浓度达到41.84ng/cm2，环磷酰胺为0.98ng/cm2；其次为病区药箱，环磷酰胺平均污染浓度为19.05ng/cm2，阿糖胞苷为0.69ng/cm2；再次为药架，环磷酰胺平均污染浓度为9.75ng/cm2，阿糖胞苷为0.73ng/cm2。口罩外侧的环磷酰胺和阿糖胞苷的检出率为100%和60%，平均校正污染量分别为2.43ng/张和1.82ng/张，口罩内侧污染率低于10%。佩戴两层乳胶手套时，最外侧手套环磷酰胺和阿糖胞苷的平均校正污染量分别为176.96ng/副和123.03ng/副，内侧分别为25.05ng/副和9.51ng/副。佩戴四层手套后，环磷酰胺内侧污染量仅为1.84ng/副，阿糖胞苷浓度全部低于定量限。（3）建立了UPLC-MS/MS测定工作人员尿液中环磷酰胺浓度的方法，并进行了方法学确证，尿中杂质不干扰样品的测定，在20~10000pg·mL~(-1)浓度范围内线性关系良好（R2=0.9981），批内批间精密度、回收率、基质效应、稳定性均符合生物样本检测要求。暴露组30份工作后的尿液中有3份测出有环磷酰胺，浓度分别为217.4、526.9、159.7pg·mL~(-1)。（4）暴露组和控制组人员的淋巴细胞早期凋亡率分别为（10.17±4.00）%和（7.87±2.97）%，P=0.02，结果表明两组人员DNA损伤程度的比较有统计学意义；暴露组和控制组的人员尿液8-OHdG的浓度分别为14.86±8.41（4.5-38.92）ng/mg Cr和9.67±4.80（2.32-22.9）ng/mg Cr，P=0.0047，显示两组人员尿液氧化损伤程度有显著差异；微量波动法结果：暴露组TA98的低、中、高剂量的尿液致突变阳性率分别为21.8%、56.3%、75%，高于控制组11.1%、41.7%和66.7%，暴露组TA100低、中、高尿液致突变阳性率分别为21.9%、53.1%、78.1%，高于控制组的16.7%、44.4%和63.9%。结论：抗肿瘤药物在PIVAS环境中存在一定范围的污染，调配人员在处置抗肿瘤药物时，频繁接触抗肿瘤药物可能对人体造成损伤，提示需要加强PIVAS中抗肿瘤药物职业暴露的防范。
[Abstract]:Objective: to assess the exposure of anti tumor drugs in the working environment through environmental monitoring and biological monitoring of the anti tumor drug allocation area of PIVAS, and to provide the basis for the management of the government departments and medical institutions against the management of cancer drug allocation.
Methods: (1) 30 pharmacists who were exposed to antitumor drugs in PIVAS of a three a hospital were selected as the exposure group, and 30 health workers who did not have contact with the antitumor drug were used as the control group. The basic information of age, sex, diet, smoking, work position, working life, protection measures and other basic information were collected by questionnaire. (2) environment. Test: select cyclophosphamide, cytarabine as a biomarker for environmental monitoring, use super high performance liquid phase tandem mass spectrometry (UPLC-MS/MS) to determine the residual concentrations of antitumor drugs in different environmental cleaning samples of hospital PIVAS and the mediator and inside and outside of the mask. (3) biological monitoring: the determination of urine cyclophosphamide by UPLC-MS/MS After Annexin-V-PI double staining, the rate of lymphocyte apoptosis was detected by flow cytometry; the urine 8-OHdG/Cr value was measured by enzyme linked immunosorbent assay (Elisa), and the mutagenicity test of urine concentrate was carried out by TA98 and TA100 of typhus typhimurium.
Results: (1) the basic data of the subjects were analyzed and compared respectively. There was no statistical difference between the exposure group and the control group in age, sex, diet and smoking. The baseline was balanced and comparable.
(2) a method for the determination of cytosine and cytarabine in the wiped samples by UPLC-MS/MS was established, and a methodological confirmation that the biological safety cabinet in.PIVAS, the ground, the drug shelf, the drug box, the telephone, the refrigerator handle and the door handle of the transfer bin were all polluted by different degrees of cyclophosphamide and cytarabine. The most serious pollution was the operation of biological safety cabinet. On the table, the average pollution concentration of cytarabine was 41.84ng/cm2, cyclophosphamide was 0.98ng/cm2, followed by the case area medicine box, the average pollution concentration of cyclophosphamide was 19.05ng/cm2, Ara cytidine was 0.69ng/cm2; again the drug shelf, the average pollution concentration of cyclophosphamide was 9.75ng/cm2, cytarabine was the cyclophosphamide and opioid on the outside of 0.73ng/cm2. mask. The detection rates of cytosine cytosine were 100% and 60%, the average correction of pollution was 2.43ng/ and 1.82ng/, and the inner contamination rate of the masks was lower than that of 10%. wearing two layers of latex gloves. The average correction pollution of the most lateral glove cyclophosphamide and cytarabine were 176.96ng/ pair and 123.03ng/ pair respectively. The inner side of the glove was 25.05ng/ and 9.51ng/, respectively. After four layers of gloves, the internal contamination of cyclophosphamide was only 1.84ng/ pairs, and the cytosine arabinoside concentration was below the limit of quantification.
(3) a method was established to determine the concentration of cyclophosphamide in urine of the staff by UPLC-MS/MS. The method was confirmed by methodology. The urine impurities did not interfere with the determination of samples. The linear relationship was good (R2=0.9981) in the concentration range of 20~10000pg mL~ (-1). The precision, recovery rate, matrix effect and stability in batch batch were in line with the requirements of biological sample detection. In the exposure group, 3 of the urine samples were tested for cyclophosphamide, with a concentration of 217.4526.9159.7pg. ML~ (-1) after 30 jobs.
(4) the early apoptosis rate of lymphocytes in the exposure group and control group was (10.17 + 4)% and (7.87 + 2.97)%, P=0.02. The results showed that the degree of DNA injury in the two groups was statistically significant, and the urine 8-OHdG concentration in the exposed and control groups was 14.86 + 8.41 (4.5-38.92) ng/mg Cr and 9.67 + 4.80 (2.32-22.9) ng/mg Cr, respectively. P=0.0047 showed a significant difference in the degree of oxidative damage in the urine of the two groups, and the results of trace fluctuation: the positive rates of urine induced mutations in the exposed group TA98 were 21.8%, 56.3%, 75%, respectively, 11.1%, 41.7% and 66.7% in the control group, and the low TA100 in the exposed group, and the positive rates of high urine mutation were 21.9%, 53.1%, 78.1%, respectively, higher than the control group. 16.7%, 44.4%, and 63.9%. of the group
Conclusion: antitumor drugs have a certain extent of pollution in the PIVAS environment, and the frequent exposure to antitumor drugs may cause damage to the human body when the agents are disposed of antitumor drugs, suggesting that the prevention of occupational exposure to antitumor drugs in PIVAS should be strengthened.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R134

【参考文献】