基于ICP-MS技術(shù)對貧鈾溶解性能及血樣中鉑的測定方法的研究
發(fā)布時間：2018-08-21 08:02
【摘要】：鈾是一種同時具有放射毒性和化學(xué)毒性的重金屬。天然鈾廣泛存在于水、食物和空氣中。貧鈾(Depleted Uranium，DU)是天然鈾提取~(235)U后的副產(chǎn)品，它與天然鈾在同位素組成上有很大不同，天然鈾中~(235)U含量約為0.7%，貧鈾中~(235)U的含量是其1/3左右(0.2%~0.3%)。與天然鈾一樣，DU是放射性重金屬，其輻射強度約為天然鈾的60%。 貧鈾屬于長壽命核素，半衰期長達4.5×10~9年(以~(238)U計)，它與天然鈾一樣，同時具有放射性和重金屬毒性，進入體內(nèi)后，會對腎臟、肺、免疫系統(tǒng)和神經(jīng)系統(tǒng)有不同程度的損害。貧鈾因其密度高、易自燃、價格低廉等優(yōu)點，在商業(yè)和軍事領(lǐng)域用途廣泛。貧鈾武器最初被應(yīng)用于海灣戰(zhàn)爭，并自此被廣泛應(yīng)用于現(xiàn)代戰(zhàn)爭，戰(zhàn)后參加過作戰(zhàn)任務(wù)的士兵相繼患上了“海灣戰(zhàn)爭綜合征”，引起了人們對貧鈾使用后對人類健康和環(huán)境影響的關(guān)注。公眾攝取鈾的途徑主要來自食物和飲水，被污染的土壤和水源中的鈾可通過食用受污染的動植物或直接吸入等方式進入人體，從而對健康造成危害。因此，當(dāng)貧鈾進入環(huán)境中后，其在水體中的溶解性能和在土壤中的遷移規(guī)律對評價其健康危害，以及對鈾污染修復(fù)治理均有重要的指導(dǎo)意義。 本研究通過貧鈾氧化物的靜態(tài)溶解實驗和土柱遷移模擬實驗，對貧鈾氧化物在水環(huán)境中的溶解性能和在土壤中的遷移規(guī)律分別進行了探究。研究中采用ICP-MS技術(shù)，同時測定樣品中的鈾濃度和~(235)U/~(238)U比值，以此判斷貧鈾的存在。 ICP-MS因其檢出限低、靈敏度高、樣品用量少等優(yōu)點，在金屬元素痕量分析方面具有無可替代的優(yōu)越性。鉑類藥物是迄今為止應(yīng)用最廣泛的抗腫瘤藥之一。在該類藥物的研究過程中，建立藥代動力學(xué)模型，研究用藥后藥物在體內(nèi)的分布情況和代謝規(guī)律十分必要。鉑類藥物代謝實驗中所采集到的樣本量通常很少，在目前測定生物樣品中鉑的方法中，電感耦合等離子體質(zhì)譜（ICP-MS）法可以充分滿足樣品測定需求。本研究應(yīng)用ICP-MS技術(shù)建立了血漿中的鉑含量的測定方法，該法可以滿足鉑類藥物在大鼠和比格犬體內(nèi)藥代動力學(xué)研究的需要。 本文主要包括三個部分內(nèi)容： 一、貧鈾氧化物溶解性能的初步研究 本研究通過貧鈾氧化物的靜態(tài)溶解實驗，對貧鈾在正常降雨和模擬酸雨條件下的溶解情況，以及土壤和腐殖酸對貧鈾溶解性能的影響進行了考察。分析時采用ICP-MS技術(shù)，同時測定樣品中的鈾濃度和~(235)U/~(238)U比值，以此判斷貧鈾的溶解情況。 實驗分為正常降雨和模擬酸雨(pH=4)兩種條件，每種條件下設(shè)置三個實驗組，分別為貧鈾組、貧鈾+土壤組和貧鈾+腐殖酸組，另外在兩種條件下分別設(shè)置土壤和腐殖酸的空白組。實驗中所用的貧鈾氧化物有兩種，分別為現(xiàn)場采集的DU氧化物粉末樣品和分析純的八氧化三鈾。實驗結(jié)果顯示：對實驗組上清液最終pH值進行測定，除了含有腐殖酸的組呈弱酸性以外，其余組呈堿性。在不同時間點對各實驗組上清液取樣測定其鈾濃度和~(235)U/~(238)U值，各實驗組的比值結(jié)果集中于0.003~0.004范圍內(nèi)，與所添加的貧鈾氧化物樣品的比值一致。各實驗組鈾濃度結(jié)果顯示，單獨貧鈾粉末在上清液中的溶解度隨溶液初始酸度增加而增大；當(dāng)土壤存在時，初始一段時間內(nèi)，貧鈾在模擬酸雨中的溶解速度低于水中，在足夠的時間后，貧鈾在酸中的累積溶解量會超出水中；當(dāng)腐殖酸存在時，貧鈾溶解量均很低，至少為單獨貧鈾組溶解量的幾十分之一。實驗還發(fā)現(xiàn)在正常降雨和模擬酸雨條件下八氧化三鈾都比DU氧化物樣品具有更好的溶解性能。實驗結(jié)果說明確實有貧鈾氧化物溶解進入了上清液中；酸度增大會提高貧鈾的溶解度；在足夠的時間條件下土壤的存在能夠提高貧鈾的溶解性能；腐殖酸對貧鈾溶解有強烈抑制作用。現(xiàn)場采集的DU氧化物樣品中含有的大量雜質(zhì)成分包裹或鑲嵌在鈾氧化物的周圍，且其中的鈾氧化物粒徑大小不一；而八氧化三鈾成分單一，粒徑均勻，這些形態(tài)和成分的差異導(dǎo)致八氧化三鈾的溶解性能更好。 二、酸雨條件下腐殖酸對貧鈾氧化物在土壤中遷移的影響 鈾在土壤中的遷移會受到酸雨和土壤中腐殖酸的影響。在前期研究結(jié)果的基礎(chǔ)上，本研究進行了模擬酸雨條件下的實驗室模擬土柱實驗，對酸雨和腐殖酸二者綜合作用條件下貧鈾氧化物在土壤中的遷移情況進行了研究。 實驗中所用貧鈾氧化物仍為兩種，分別為現(xiàn)場采集的DU氧化物樣品和分析純的八氧化三鈾，各設(shè)置6個實驗組，用pH=4和pH=3的模擬酸雨分別淋洗不添加HA，添加2%HA和添加5%HA的土壤，以土層中土壤的鈾濃度和~(235)U/~(238)U同位素比值綜合判定貧鈾遷移深度。實驗結(jié)果顯示，在pH=4的模擬酸雨淋洗條件下，添加HA的組遷移深度大于不添加HA的組，添加2%HA的組遷移深度最大，這一規(guī)律與之前報道的正常降雨條件下一致；而在pH=3的模擬酸雨淋洗條件下，添加HA的組遷移深度卻小于不添加HA的組，添加5%HA的組遷移深度最小。在pH值為4的模擬酸雨條件下，HA使貧鈾在土壤中的遷移深度增大，有促進貧鈾遷移的作用，2%HA組比5%HA組促進效果明顯；而在pH值為3的酸雨條件下，HA使貧鈾在土壤中的遷移深度減小，有抑制貧鈾遷移的作用，5%HA組比2%HA組抑制效果明顯。說明酸雨淋洗條件下HA對貧鈾遷移的影響不僅與土壤中HA的含量有關(guān)，而且與酸度有關(guān)。在同樣的實驗條件下，現(xiàn)場采集的DU氧化物樣品和八氧化三鈾在土壤中的遷移規(guī)律是一致的，但是DU氧化物樣品在土壤中的遷移深度要比八氧化三鈾小。這是由于DU氧化物樣品中有較多的雜質(zhì)包裹或鑲嵌在鈾氧化物的周圍，使DU氧化物樣品在淋洗液中的溶解度降低。所有的實驗組中，無論貧鈾遷移深度的大小，仍然有90%以上的貧鈾集中于表層2cm的土層內(nèi)。說明對于落在土壤表面的貧鈾氣溶膠，經(jīng)過遷移而能達到較大垂直深度的貧鈾量是很少的，絕大部分的貧鈾仍會停留在土壤的表層。 三、建立ICP-MS測定血漿中鉑含量的方法 本研究應(yīng)用ICP-MS技術(shù)建立了血漿中的鉑含量的測定方法，該法可以滿足鉑類藥物在大鼠和比格犬體內(nèi)藥代動力學(xué)研究的需要。 實驗采用直接稀釋法處理血漿樣品，樣品用量少，操作簡便。以Ir作為內(nèi)標(biāo)元素，Pt元素標(biāo)準(zhǔn)曲線在2~250μg·L~(-1)濃度范圍內(nèi)線性良好，r≥0.9996。測定過程采用自動進樣器進樣，分析速度快，，分析過程中內(nèi)標(biāo)元素Ir的計數(shù)穩(wěn)定（RSD5%），最低檢出限低。方法的準(zhǔn)確度高，相對誤差在±5%范圍內(nèi)，方法的日內(nèi)精密度和日間精密度高，RSD4.0%。經(jīng)稀釋處理的血漿樣品在4℃放置24h、-20℃放置24h凍融和室溫放置24h三種條件下的穩(wěn)定性均好，樣品測定準(zhǔn)確度高，相對誤差在±10%范圍內(nèi)。采用本方法對Wistar大鼠/比格犬血漿樣品進行測定，得到了血漿中鉑濃度-時間代謝曲線，結(jié)果令人滿意。本方法同時適用于血漿超濾樣品中鉑濃度的測定，可以滿足鉑類藥物的臨床前藥代動力學(xué)研究的需要。
[Abstract]:Uranium is a heavy metal with both radiotoxicity and chemical toxicity. Natural uranium is widely found in water, food and air. Depleted uranium (DU) is a by-product of extraction of ~ (235) U from natural uranium. It differs greatly from natural uranium in isotope composition. The content of ~ (235) U in natural uranium is about 0.7%, and that of ~ (235) U in depleted uranium is 1. /3 or so (0.2%~0.3%). Like natural uranium, DU is a radioactive heavy metal whose radiation intensity is about 60%. of natural uranium.
Depleted uranium is a long-lived nuclide with a half-life of 4.5 65 Depleted uranium weapons were originally used in the Gulf War and have since been widely used in modern warfare. Soldiers who participated in post-war operations have developed the Gulf War Syndrome, which has aroused concern about the health and environmental impact of depleted uranium after use. The public's access to uranium comes mainly from food and drinking water. Uranium in contaminated soil and water can enter human body by eating contaminated plants and animals or by direct inhalation, which is harmful to human health. Therefore, when depleted uranium enters the environment, its solubility in water and its migration in soil are important for evaluating its health hazards and remediation of uranium pollution. Guiding significance.
In this study, the solubility of depleted uranium oxides in water and the migration of depleted uranium oxides in soil were studied by static dissolution experiment and soil column migration simulation experiment.
ICP-MS has irreplaceable advantages in trace analysis of metal elements because of its low detection limit, high sensitivity and low sample dosage. Platinum drugs are one of the most widely used antineoplastic drugs so far. In the course of the study of these drugs, pharmacokinetic models were established to study the distribution of the drugs in vivo. The amount of samples collected in the experiment of platinum metabolism is usually very small. Among the current methods for the determination of platinum in biological samples, inductively coupled plasma mass spectrometry (ICP-MS) can fully meet the needs of sample determination. To meet the needs of pharmacokinetics of platinum drugs in rats and beagles.
This article mainly includes three parts:
A preliminary study on the solubility of depleted uranium oxides
In this study, the dissolution of depleted uranium under normal and simulated acid rain conditions and the effect of soil and humic acid on the dissolution of depleted uranium were investigated by static dissolution experiments of depleted uranium oxides. Situation.
The experiment was divided into two conditions: normal rainfall and simulated acid rain (pH=4). Under each condition, three experimental groups were set up, namely depleted uranium group, depleted uranium + soil group and depleted uranium + humic acid group. In addition, a blank group of soil and humic acid was set up under the two conditions. The results showed that the final pH value of the supernatant of the experimental group was determined, except that the group containing humic acid was weak acidic, the other groups were alkaline. In the range of 0.003-0.004, the ratio of depleted uranium oxide to the added depleted uranium oxide is the same. The results of uranium concentration in each experimental group show that the solubility of depleted uranium powder in supernatant increases with the increase of initial acidity of the solution; in the presence of soil, the dissolution rate of depleted uranium in simulated acid rain is lower than that in water for an initial period of time, when it is sufficient. In addition, the cumulative solubility of depleted uranium in acid is higher than that in water. When humic acid exists, the solubility of depleted uranium is very low, at least one-tenth of that in a single depleted uranium group. There are depleted uranium oxides dissolved into the supernatant; the solubility of depleted uranium increases with the increase of acidity; the solubility of depleted uranium can be improved with the presence of soil in sufficient time; humic acid has a strong inhibitory effect on the dissolution of depleted uranium. A large number of impurities in the DU oxide samples collected in the field are encapsulated or embedded in it. Uranium oxide is surrounded by uranium oxide and the particle size of uranium oxide is different, while uranium oxide has a single composition and a uniform particle size. The difference of these morphologies and compositions leads to better solubility of uranium oxide.
Two, the effect of humic acid on the migration of depleted uranium oxides in soil under acid rain.
Uranium migration in soils is affected by acid rain and humic acid in soils. On the basis of previous research results, laboratory simulated soil column experiments under simulated acid rain conditions were carried out to study the migration of depleted uranium oxides in soils under the combined action of acid rain and humic acid.
The depleted uranium oxides used in the experiment are still two kinds, one is DU oxides sampled in situ and the other is analytical pure uranium trioxide. Six experimental groups are set up respectively. The soils with and without HA, 2% HA and 5% HA are leached by simulated acid rain with pH=4 and pH=3, respectively. The uranium concentration and ~ (235) U/~ (238) U isotope ratio in the soils are determined comprehensively. Depleted Uranium Migration depth. The results showed that the migration depth of HA-added group was greater than that of HA-not-added group under simulated acid rain leaching condition of pH=4, and that of 2% HA-added group was the largest, which was consistent with the previous reported normal rainfall condition. However, the migration depth of HA-added group was less than that of acid rain leaching condition of pH=3. Under simulated acid rain with pH 4, HA increased the migration depth of depleted uranium in the soil and promoted the migration of depleted uranium. The migration depth of depleted uranium in the 2% HA group was significantly higher than that in the 5% HA group, but the migration depth of depleted uranium in the soil was decreased and the depleted uranium was inhibited under acid rain with pH 3. The migration of depleted uranium in 5% HA group was significantly inhibited than that in 2% HA group, indicating that the effect of HA on the migration of depleted uranium under acid rain leaching was not only related to the content of HA in soil, but also related to acidity. The solubility of DU oxides in the leaching solution is reduced due to the inclusion of more impurities in the DU oxides or their enclosure around the uranium oxides. In all the experimental groups, more than 90% of the depleted uranium is concentrated on the surface regardless of the depleted uranium migration depth. It is shown that for depleted uranium aerosols falling on the soil surface, the amount of depleted uranium that can reach a greater vertical depth by migration is very small, and most of the depleted uranium will remain on the surface of the soil.
Three, establish a ICP-MS method for the determination of platinum in plasma.
A method for the determination of platinum in plasma was developed by ICP-MS. The method can meet the requirements of pharmacokinetic studies of platinum drugs in rats and beagles.
Using Ir as internal standard element, the standard curve of Pt element has a good linearity in the range of 2~250 ug.L~(-1) concentration, R (>0.9996). The automatic sampler is used in the determination process. The analysis speed is fast, the internal standard element Ir count is stable (RSD 5%) and the lowest detection rate is obtained. The method has high accuracy and relative error within (+) 5%. The intra-day precision and inter-day precision of the method are 4.0%. The diluted plasma samples have good stability under the conditions of 4 (?) C for 24 hours, - 20 (?) C for 24 hours and room temperature for 24 hours. The determination accuracy of the samples is high and the relative error is within (?) 10%. The method was applied to the determination of platinum concentration in plasma samples of Wistar rats/Beagle dogs with satisfactory results. The method is also suitable for the determination of platinum concentration in plasma ultrafiltration samples and can meet the needs of preclinical pharmacokinetic studies of platinum drugs.
【學(xué)位授予單位】：中國人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R144;X132
本文編號：2195072
[Abstract]:Uranium is a heavy metal with both radiotoxicity and chemical toxicity. Natural uranium is widely found in water, food and air. Depleted uranium (DU) is a by-product of extraction of ~ (235) U from natural uranium. It differs greatly from natural uranium in isotope composition. The content of ~ (235) U in natural uranium is about 0.7%, and that of ~ (235) U in depleted uranium is 1. /3 or so (0.2%~0.3%). Like natural uranium, DU is a radioactive heavy metal whose radiation intensity is about 60%. of natural uranium.
Depleted uranium is a long-lived nuclide with a half-life of 4.5 65 Depleted uranium weapons were originally used in the Gulf War and have since been widely used in modern warfare. Soldiers who participated in post-war operations have developed the Gulf War Syndrome, which has aroused concern about the health and environmental impact of depleted uranium after use. The public's access to uranium comes mainly from food and drinking water. Uranium in contaminated soil and water can enter human body by eating contaminated plants and animals or by direct inhalation, which is harmful to human health. Therefore, when depleted uranium enters the environment, its solubility in water and its migration in soil are important for evaluating its health hazards and remediation of uranium pollution. Guiding significance.
In this study, the solubility of depleted uranium oxides in water and the migration of depleted uranium oxides in soil were studied by static dissolution experiment and soil column migration simulation experiment.
ICP-MS has irreplaceable advantages in trace analysis of metal elements because of its low detection limit, high sensitivity and low sample dosage. Platinum drugs are one of the most widely used antineoplastic drugs so far. In the course of the study of these drugs, pharmacokinetic models were established to study the distribution of the drugs in vivo. The amount of samples collected in the experiment of platinum metabolism is usually very small. Among the current methods for the determination of platinum in biological samples, inductively coupled plasma mass spectrometry (ICP-MS) can fully meet the needs of sample determination. To meet the needs of pharmacokinetics of platinum drugs in rats and beagles.
This article mainly includes three parts:
A preliminary study on the solubility of depleted uranium oxides
In this study, the dissolution of depleted uranium under normal and simulated acid rain conditions and the effect of soil and humic acid on the dissolution of depleted uranium were investigated by static dissolution experiments of depleted uranium oxides. Situation.
The experiment was divided into two conditions: normal rainfall and simulated acid rain (pH=4). Under each condition, three experimental groups were set up, namely depleted uranium group, depleted uranium + soil group and depleted uranium + humic acid group. In addition, a blank group of soil and humic acid was set up under the two conditions. The results showed that the final pH value of the supernatant of the experimental group was determined, except that the group containing humic acid was weak acidic, the other groups were alkaline. In the range of 0.003-0.004, the ratio of depleted uranium oxide to the added depleted uranium oxide is the same. The results of uranium concentration in each experimental group show that the solubility of depleted uranium powder in supernatant increases with the increase of initial acidity of the solution; in the presence of soil, the dissolution rate of depleted uranium in simulated acid rain is lower than that in water for an initial period of time, when it is sufficient. In addition, the cumulative solubility of depleted uranium in acid is higher than that in water. When humic acid exists, the solubility of depleted uranium is very low, at least one-tenth of that in a single depleted uranium group. There are depleted uranium oxides dissolved into the supernatant; the solubility of depleted uranium increases with the increase of acidity; the solubility of depleted uranium can be improved with the presence of soil in sufficient time; humic acid has a strong inhibitory effect on the dissolution of depleted uranium. A large number of impurities in the DU oxide samples collected in the field are encapsulated or embedded in it. Uranium oxide is surrounded by uranium oxide and the particle size of uranium oxide is different, while uranium oxide has a single composition and a uniform particle size. The difference of these morphologies and compositions leads to better solubility of uranium oxide.
Two, the effect of humic acid on the migration of depleted uranium oxides in soil under acid rain.
Uranium migration in soils is affected by acid rain and humic acid in soils. On the basis of previous research results, laboratory simulated soil column experiments under simulated acid rain conditions were carried out to study the migration of depleted uranium oxides in soils under the combined action of acid rain and humic acid.
The depleted uranium oxides used in the experiment are still two kinds, one is DU oxides sampled in situ and the other is analytical pure uranium trioxide. Six experimental groups are set up respectively. The soils with and without HA, 2% HA and 5% HA are leached by simulated acid rain with pH=4 and pH=3, respectively. The uranium concentration and ~ (235) U/~ (238) U isotope ratio in the soils are determined comprehensively. Depleted Uranium Migration depth. The results showed that the migration depth of HA-added group was greater than that of HA-not-added group under simulated acid rain leaching condition of pH=4, and that of 2% HA-added group was the largest, which was consistent with the previous reported normal rainfall condition. However, the migration depth of HA-added group was less than that of acid rain leaching condition of pH=3. Under simulated acid rain with pH 4, HA increased the migration depth of depleted uranium in the soil and promoted the migration of depleted uranium. The migration depth of depleted uranium in the 2% HA group was significantly higher than that in the 5% HA group, but the migration depth of depleted uranium in the soil was decreased and the depleted uranium was inhibited under acid rain with pH 3. The migration of depleted uranium in 5% HA group was significantly inhibited than that in 2% HA group, indicating that the effect of HA on the migration of depleted uranium under acid rain leaching was not only related to the content of HA in soil, but also related to acidity. The solubility of DU oxides in the leaching solution is reduced due to the inclusion of more impurities in the DU oxides or their enclosure around the uranium oxides. In all the experimental groups, more than 90% of the depleted uranium is concentrated on the surface regardless of the depleted uranium migration depth. It is shown that for depleted uranium aerosols falling on the soil surface, the amount of depleted uranium that can reach a greater vertical depth by migration is very small, and most of the depleted uranium will remain on the surface of the soil.
Three, establish a ICP-MS method for the determination of platinum in plasma.
A method for the determination of platinum in plasma was developed by ICP-MS. The method can meet the requirements of pharmacokinetic studies of platinum drugs in rats and beagles.
Using Ir as internal standard element, the standard curve of Pt element has a good linearity in the range of 2~250 ug.L~(-1) concentration, R (>0.9996). The automatic sampler is used in the determination process. The analysis speed is fast, the internal standard element Ir count is stable (RSD 5%) and the lowest detection rate is obtained. The method has high accuracy and relative error within (+) 5%. The intra-day precision and inter-day precision of the method are 4.0%. The diluted plasma samples have good stability under the conditions of 4 (?) C for 24 hours, - 20 (?) C for 24 hours and room temperature for 24 hours. The determination accuracy of the samples is high and the relative error is within (?) 10%. The method was applied to the determination of platinum concentration in plasma samples of Wistar rats/Beagle dogs with satisfactory results. The method is also suitable for the determination of platinum concentration in plasma ultrafiltration samples and can meet the needs of preclinical pharmacokinetic studies of platinum drugs.
【學(xué)位授予單位】：中國人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R144;X132
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