本文選題：抗腫瘤藥物 + 職業(yè)暴露　； 參考：《蘇州大學》2013年碩士論文

【摘要】：目的：通過對靜脈藥物調(diào)配中心（PIVAS）抗腫瘤藥物配置區(qū)域進行環(huán)境監(jiān)測與生物監(jiān)測，評估集中調(diào)配人員在工作環(huán)境中抗腫瘤藥物的暴露情況，旨在為政府部門和醫(yī)療機構(gòu)對抗腫瘤藥物配置的管理提供依據(jù)。 方法：（1）選擇某三甲醫(yī)院PIVAS中30名接觸抗腫瘤藥物配置的藥學人員為暴露組，30名不接觸抗腫瘤藥物配置的健康人員作為控制組，通過問卷調(diào)查收集人員的年齡、性別、飲食、吸煙情況、工作崗位、工作年限、防護措施等基本信息。（2）環(huán)境檢測：選擇環(huán)磷酰胺、阿糖胞苷為環(huán)境監(jiān)測的生物標記物，用超高效液相串聯(lián)質(zhì)譜法（UPLC-MS/MS）測定醫(yī)院PIVAS不同的環(huán)境擦拭樣本和調(diào)配人員手套和口罩內(nèi)側(cè)及外側(cè)的抗腫瘤藥物的殘留濃度。（3）生物監(jiān)測：用UPLC-MS/MS測定尿液環(huán)磷酰胺的濃度；采用Annexin-V-PI雙染色后，流式細胞儀檢測淋巴細胞凋亡率；酶聯(lián)免疫吸附測定（Elisa）法測定尿液8-OHdG/Cr值；利用鼠傷寒桿菌TA98和TA100分別對尿濃縮液進行致突變的微量波動試驗。 結(jié)果：（1）分別對調(diào)查對象的基本資料進行分析比較，暴露組和控制組在年齡、性別、飲食、吸煙情況均無統(tǒng)計學差異，，基線均衡，具有可比性。 （2）建立了UPLC-MS/MS測定擦拭樣本中環(huán)磷酰胺和阿糖胞苷濃度的方法，并進行了方法學確證。PIVAS中生物安全柜、地面、藥架、藥箱、電話、冰箱把手、傳遞倉門把手均存在不同程度的環(huán)磷酰胺和阿糖胞苷污染。污染最嚴重的是生物安全柜操作臺面，阿糖胞苷平均污染濃度達到41.84ng/cm2，環(huán)磷酰胺為0.98ng/cm2；其次為病區(qū)藥箱，環(huán)磷酰胺平均污染濃度為19.05ng/cm2，阿糖胞苷為0.69ng/cm2；再次為藥架，環(huán)磷酰胺平均污染濃度為9.75ng/cm2，阿糖胞苷為0.73ng/cm2。口罩外側(cè)的環(huán)磷酰胺和阿糖胞苷的檢出率為100%和60%，平均校正污染量分別為2.43ng/張和1.82ng/張，口罩內(nèi)側(cè)污染率低于10%。佩戴兩層乳膠手套時，最外側(cè)手套環(huán)磷酰胺和阿糖胞苷的平均校正污染量分別為176.96ng/副和123.03ng/副，內(nèi)側(cè)分別為25.05ng/副和9.51ng/副。佩戴四層手套后，環(huán)磷酰胺內(nèi)側(cè)污染量僅為1.84ng/副，阿糖胞苷濃度全部低于定量限。 （3）建立了UPLC-MS/MS測定工作人員尿液中環(huán)磷酰胺濃度的方法，并進行了方法學確證，尿中雜質(zhì)不干擾樣品的測定，在20~10000pg·mL~(-1)濃度范圍內(nèi)線性關(guān)系良好（R2=0.9981），批內(nèi)批間精密度、回收率、基質(zhì)效應、穩(wěn)定性均符合生物樣本檢測要求。暴露組30份工作后的尿液中有3份測出有環(huán)磷酰胺，濃度分別為217.4、526.9、159.7pg·mL~(-1)。 （4）暴露組和控制組人員的淋巴細胞早期凋亡率分別為（10.17±4.00）%和（7.87±2.97）%，P=0.02，結(jié)果表明兩組人員DNA損傷程度的比較有統(tǒng)計學意義；暴露組和控制組的人員尿液8-OHdG的濃度分別為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，顯示兩組人員尿液氧化損傷程度有顯著差異；微量波動法結(jié)果：暴露組TA98的低、中、高劑量的尿液致突變陽性率分別為21.8%、56.3%、75%，高于控制組11.1%、41.7%和66.7%，暴露組TA100低、中、高尿液致突變陽性率分別為21.9%、53.1%、78.1%，高于控制組的16.7%、44.4%和63.9%。 結(jié)論：抗腫瘤藥物在PIVAS環(huán)境中存在一定范圍的污染，調(diào)配人員在處置抗腫瘤藥物時，頻繁接觸抗腫瘤藥物可能對人體造成損傷，提示需要加強PIVAS中抗腫瘤藥物職業(yè)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.
【學位授予單位】：蘇州大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R134

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