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2019年12月英语六级试卷及解答（第一套）Part Ⅰ Writing (30 minutes) Directions: For this part, you are allowed 30 minutes to write an essay on the importance of having a sense of community responsibility. You should write at least 150 words but no more than 200 words.【参照范文】There is no doubt that community responsibility plays an indispensable role in personal development, for instance, in the workplace.There are several factors accounting for this perspective and the following are the most typical ones. First and foremost, a strong sense of community responsibility is helpful to develop harmonious interpersonal relationships. As we all know, we are very likely to spend more time with our colleagues than our families after entering the workplace. Therefore, the sound wor atmosphere and interpersonal relationships among employees are crucial to both physical and mental pleasure. In addition, community responsibility can improve efficiency. In the fast-paced modern society, time is money and efficiency holds the key to saving time. As the saying goes, two heads are better than one. So great importance should be attached to the cultivation of the sense of community responsibility and we will eventually benefit from it.From what has been mentioned above, we can come to the conclusion that the sense of community responsibility is a kind of good personal quality, which deserves our attention.【参照译文】毫无疑问，集体责任在个人发展中起着不可或缺的作用，例如在工作场所。
第三章 药物代谢与转运及其临床意义1. 熟悉药物代谢与药动学的关系、常见代谢反应类型、影响药物代谢的因素、转运蛋白介导药物相互作用的机制。
2. 掌握常见一相和二相代谢酶的分类和作用、药物代谢酶多态性与临床个体化用药的关系、转运蛋白分类及其体内过程中的作用。
3. 了解常见代谢酶的底物、抑制剂和诱导剂、药物代谢酶遗传多态性与疾病易感性的关系、同类药品的代谢特点差异、转运蛋白多态性及其对临床用药的影响。
药物代谢（Drug metabolism），或称生物转化（Biotransformation），是药物在体内发生的化学结构改变，是药物进入机体后机体对药物进行处置的重要环节。
通过药物代谢这一环节，可以产生四个方面的结果：即①转化为无活性物；②使原来无药理活性的药物转变为有活性的代谢物；③将活性药物转化为其他活性物质；④产生毒性物质。
最终机体还要通过各种途径终止药物的这些作用。
怎样才能终止呢？当药物进入体内后，机体对一些小分子的药物或者具极性的药物分子，大部分可以经肾或胆汁系统，从尿液或粪便排出体外。
但是大多数药物为亲脂性，在生理pH条件下仅部分解离或完全不解离，而且又常常与血浆蛋白结合，因此不易从肾小球滤过；另一方面由于肾小管膜具亲脂性，又使得这类经肾小球滤过的药物易于被肾小管重吸收。
所以，如果这些药物仅仅靠肾脏排泄，则其生物半衰期将会变得很长。
这种情况下机体内另一种可以终止药物作用的过程——药物代谢便可发挥重要作用。
通常亲脂性的药物可以通过药物代谢变成极性较强、更易于由肾排泄的产物。
例如，脂溶性的巴比妥类药物例如硫喷妥钠（Thiopental sodium）或苯巴比妥（Phenobarbital），假如不是通过药物代谢成水溶性物质的话，则其生物半衰期（Biological half-life）将会长达100年以上。
表3-1列举了理想药物应具备的特性。
其中第2～9条即与药物代谢密切有关。
Table3.1 Properties of an “ideal” drug1. Good aqueous solubility（IV formulation/oral absorption）2. Acceptable (linear) pharmacokinetics3.”Balanced” clearance－Renal excretion of parent drug－Biliary secretion of parent drug－Metabolism to a limited number of pharmacologically inactive products4. Oxidative metabolism catalyzed by several CYPs (>2)5. Oxidative metabolism should not depend largely on polymorphic CYP6. No chemically reactive metabolites7. Weak or no induction of drug-metabolizing enzymes and transporters8. Weak or no inhibition of drug-metabolizing enzymes and transporters9. Small first pass effect (gut and liver)10. Wide therapeuticindex (good potency and low dose)通过药物代谢研究，阐明药物体内代谢物的结构和代谢途径，分别对母体药物和代谢物进行药效学和毒理学比较，可以阐明药物在体内发挥药效的化学基础，了解药物在体内的药理和/或毒理情况，也为进一步改进活性药物的化学结构提供依据；阐明药物体内代谢的参与酶，将有助于理解药物代谢的机理与代谢相互作用，改造药物化学结构以开发出具备有利代谢特点的新药或设计药物的化学结构开发出影响药物代谢酶活性、具备新临床用途的药物。
2021年第10期广东化工第48卷总第444期·231·RP-HPLC法测定血浆中奥卡西平及其活性代谢物浓度刘东平，谢海燕(南京鼓楼医院集团安庆市石化医院药剂科，安徽安庆246001)Determination of the Concentration of Oxcarbazepine andIts Active Metabolites in Human Plasma by RP-HPLCLiu Dongping,Xie Haiyan(Pharmacy Department,Anqing Shihua Hospital of Nanjing Drum Tower Hospital Group,Anqing246001,China) Abstract:Objective:To establish a method for determining the concentration of Oxcarbazepine(OXC)and its active metabolite10,11-Dihydro-10-hydroxy Carbamzepine(MHD)in human plasma.Methods:We used Alprzolam as the internal standard,Plasma samples were detected by RP-HPLC after being processed by Methyl t-Butyl Ether,using a mobile phase of CH3CN-H2O(45︰55,v/v)at the flow rate of1.0mL/min.The temperature was40℃,detection wavelength was220 nm and sensitivity was0.01AUFS.Results:There was a good linear relationship in the concentration of OXC respectively in the range of0.28~4.48µg/mL and MHD respectively in the range of2.40~38.40µg/mL,the lowest limit of detection was0.35µg/mL and1.20µg/mL.The relative average recoveries of low,middle and high concentration were respectively83.23%~103.17%and87.99%~116.07%;the RSD of intra-day(n=3)and inter-day(n=5)variation were less than10%. Conclusions:The method is sensitive,accurate,easy and quick.That can be used for therapeutic drug monitoring(TDM)and pharmacokinetics studies.Keywords:OXC；MHD；therapeutic drug monitoring(TDM)；RP-HPLC奥卡西平(Oxcarbazepine,OXC)是卡马西平的10－酮基结构类似物，为前体药，在体内迅速被代谢为有药理活性的10-羟基代谢物(10-monohydroxy metaboliute，MHD)[1]，即10,11-二氢-10-羟基卡马西平(10,11-Dihydro-10-hydroxy Carbamazepine)。
中国现代医药杂志2021年1月第23卷第1期 MMJC,Jan 2021, Vol 23,No.l・79・DOI ： 10.3969彳.issn.1672-9463.2021.01.020奥卡西平片致白细胞减少1例孙博1刘勋2张二锋1马换青1奥卡西平是一种新型抗癫痫药,是卡马西平的 10-酮类衍化物叫在体内可迅速转化成活性代谢 物10-径基卡马西平发挥抗癫痫作用,2000年1月 经美国食品药品监督管理局批准在美国上市,2003年底在我国上市* ［2］o 奥卡西平用于治疗癫痫原发性 全面性强直阵挛发作和部分性发作,伴有或不伴有继发性全面性发作冈，其作用机制与卡马西平相似， 但有更好的耐受性和较小的肝药酶诱导作用［4-5］o本药代谢基本不受细胞色素P450酶系统诱导所影 响，对肝药酶、自身诱导作用十分轻微，与其他药物 联用相互作用较小问。
此外,奥卡西平还具有生物 利用率高、对肝肾功能影响小、不良反应少等优点， 使其在临床上应用广泛叫作者单位?郑州市第三人民医院药学部,河南郑州4500002郑州市第二人民医院药学部，河南郑州450000奥卡西平常见的不良反应有嗜睡、头痛等神经系统症状冈，恶心、呕吐等胃肠道不适症状叫 崔红 霞等［10］报道了 163例奥卡西平弓I 起的不良反应，其 中皮肤系统不良反应所占比例最高，多为皮疹、湿疹等。
有学者报道了奥卡西平片引起的低钠血症，认为此不良反应与奥卡西平引起的内源性抗利尿 激素增多有关［1142］o 奥卡西平被认为是对血液系 统相对较安全的药物,其所致的血液系统损害为罕见的不良反应，如全血小板减少问、贫血等。
我们发现奥卡西平片引起白细胞减少［例，现报道如下。
1临床资料患者，男,47岁，因癫痫复发于2019年10月30日入院，家属诉患者发作时意识丧失、呼之不应， 伴四肢抽搐,双眼向上凝视，牙关紧闭，口吐白沫， 半天时间患者已发作3次，每次2~3min 缓解。
患者癫痫史45年,长期口服奥卡西平片0.45g( 0.15g,Novartis Farma S.p.A),每日2次。
手性药物体外代谢的研究方法王彬;杨雷琼【摘要】手性药物体外代谢的研究是通过建立体外代谢模型对手性药物的代谢行为进行评价.随着大量手性药物的开发,出现了多种与体外代谢相关的研究方法和技术来评价对映体之间的分子以及代谢动力学方面的差异,从而选择出对映体.现对已有的一些研究方法及其优缺点进行综述,从而提供更系统化的手性药物的评选方法,更快速有效地为手性药物提供技术支持.%In vitro metabolism study of chiral drugs is to evaluate the metabolic behavior in vitro metabolic model. With the discovery of more chiral drugs, a lot of techniques and methods have been developed to evaluate chiral drug in vitro metabolism, so that molecular mechanisms and pharmacokinetic processes of two enantiomers can be displayed and the better can be selected. Here is to make a review on recent advances regarding different analytical techniques of chiral drugs and their metabolites, with the aim of offering a systemic reference for choosing suitable approach of chiral drug evaluation and selection.【期刊名称】《医学综述》【年(卷),期】2012(018)011【总页数】3页(P1614-1616)【关键词】手性药物;体外代谢;方法【作者】王彬;杨雷琼【作者单位】中国人民解放军总医院检验科,北京,100853;中国人民解放军总医院检验科,北京,100853;沈阳药科大学,沈阳,110016【正文语种】中文【中图分类】R969.1目前，在临床上应用的具有光学活性的药物已超过60%。
绝密★考试结束前2024学年第一学期浙江省七彩阳光新高考研究联盟返校联考高三英语试题考生须知：1．本试题卷共8页，满分150分，考试时间120分钟。
2．答题前，在答题卷指定区域填写班级、姓名、考场号、座位号及准考证号。
3．所有答案必须写在答题卷上，写在试卷上无效。
4．考试结束后，只需上交答题卷。
第Ⅰ卷第一部分听力（共两节，满分30分）第一节（共5小题；每小题1.5分，满分7.5分）听下面5段对话。
每段对话后有一个小题，从题中所给的A、B、C三个选项中选出最佳选项，并标在试卷的相应位置。
听完每段对话后，你都有10秒钟的时间来回答有关小题和阅读下一小题。
每段对话仅读一遍。
1．What’s probably the woman’s job?A．A hotel receptionist. B．A librarian. C．A customs officer.2．Why does the woman make the call?A．To make an application. B．To give information. C．To answer a question.3．How does Linda feel?A．Confused. B．Surprised. C．Shocked.4．What makes Jim hurry?A．Attending a lecture. B．Doing business. C．Meeting assistants.5．Which does the man prefer?A．Beef stew. B．Fried eggs. C．Fish soup.第二节（共15小题；每小题1.5分，满分22.5分）听下面5段对话或独白。
每段对话或独白后有几个小题，从题中所给的A、B、C三个选项中选出最佳选项，并标在试卷的相应位置。
听每段对话或独白前，你将有时间阅读各个小题，每小题5秒钟；听完后，各小题将给出5秒钟的作答时间。
江苏省无锡市滨湖区辅仁高级中学2024-2025学年高三上学期10月月考英语试题一、阅读理解WHEN CHOCOLATE BECOMES A WORK OF ART!Chocolate is delicious; we all know that. But it isn’t just for eating, as these chocolate works of art clearly show.Chocolate MailboxIn 2011, chocolate company Godiva made a chocolate mailbox with white truffle hearts to celebrate Valentine’s Day. The mailbox was on display at its shop on Fifth Avenue in New York City. Customers could post their love letters there, and the company would stamp and mail them for free during the three weeks leading up to Valentine’s Day.Chocolate SofaIn 2009, chocolate company Galaxy used 250 kg of their own chocolate to make a chocolate sofa. The sofa was a part of their “Irresistible Reads” campaign, which was designed to promote reading. It was put on display in Victoria Embankment Gardens in London. Photos were taken of British TV actress Emilia Fox sitting on the sofa reading a book.Chocolate TreeIn 2012, Patrick Roger made a five-metre tree from five tons of chocolate. The sculpture, which was at Roger’s shop in Paris, even had chocolate monkeys hanging from chocolate branches. Roger wanted to raise awareness of the problems facing African wildlife.Chocolate Hotel SuiteIn 2011, French chocolater Patrick Roger worked with fashion icon Karl Lagerfeld. The room, at the La Reserve hotel in Paris, had a chocolate carpet, chocolate bed and chocolate nightstand full of. chocolate books. Sitting on the bed was a chocolate man eating a Magnum ice cream.1．Which work was designed to encourage people to read?A．Chocolate Mailbox.B．Chocolate Sofa.C．Chocolate Hotel Suite.D．Chocolate Tree.2．What do Chocolate Mailbox and Chocolate Hotel Suite have in common?A．They were made to celebrate Valentine’s Day.B．They had a chocolate carpet.C．They were created in the same year.D．People could sit in them to eat ice cream.3．In which section of a magazine can we read the text?A．Entertainment.B．Nature.C．Education.D．Art.It’s May, which means that millions of students are getting ready to receive their college diplomas. Grace Bush is one of them. Grace is just 16 years old — at the age when most teenagers have not even completed high school, Grace has graduated from Florida Atlantic University (FAU) with a bachelor’s degree in criminal justice. What’s even more astonishing is that the brilliant girl received her high school diploma from Florida Atlantic High School a week after she had graduated college!While pursuing two diplomas would have been enough to keep most kids busy, Grace, who graduated with a 3.86 grade-point average, seemed to even find time to play the flute (长笛) for two bands.Though this youngest FAU graduate has attracted national attention with her unique accomplishments, for Grace, this is not deviant. That’s because she comes from a family of overachievers. Her 19-year-old sister Gisla, who is currently pursuing a master’s degree, also graduated at 16, while her 17-year-old sister Gabrielle, is already pursuing her master’s degree and is scheduled to graduate from FAU this summer.Grace’s education began when she was a toddler (刚学会走路的孩子). She learned to read by snuggling (依偎) close to her two sisters while they were being taught and was proficient by the time she turned two. From then on, her mother decided to include Grace in all the school sessions she had with her two elder sisters. Not surprisingly, by the time she turned 13, the home schooled girl was ready for high school and college.Grace plans to return to FAU in the fall to pursue a master’s degree. Following that, the young girl wants to obtain a law degree and pursue a career that she hopes will end as a judge on the US Supreme Court.4．What is Grace Bush interested in besides studying?A．Forming bands.B．Playing an instrument.C．Reading novels.D．Writing articles.5．What does the underlined word “deviant” in Paragraph 3 mean?A．Abnormal.B．Awkward.C．Visible.D．Constant.6．How did Grace Bush receive education before she was 13 years old?A．She was taught at home.B．She went to school as other kids.C．She learned from her sisters.D．She learned by herself.7．Which of the following can best describe Grace?A．Humble and humorous.B．Sporty and hardworking.C．Brilliant and ambitious.D．Shy and innocent.A recent study from SMU psychologist Sarah Kucker at Oklahoma State University, suggests shyness can influence a child’s performance in language assessments, depending on the level of social interaction required to complete the test.Shy children tend to be reserved in everyday life, including communicating with others. The study concludes that the behaviour can make accurately assessing a child’s language abilities more challenging since shy children find it harder to verbally (语言地) engage with clinicians (临床医师) and teachers than during less socially demanding tests.The research involved 122 children of varying temperaments (性格) between the ages of17 and 42 months, whose parents reported their child’s shyness using an early childhood behaviour questionnaire. Each child underwent a series of three language tasks that required different levels of social interaction: a looking task, a pointing task, and a production task that required children to say the answer verbally. In each, the children were asked to find a known object from a set of pictures.The results revealed significant differences in children’s performance across the tasks depending on shyness. Shyer children did worse on the production task than their less-shy counterparts. However, all children performed well on the pointing task regardless of their shyness level. The looking task produced a little more different results, indicating that shyer children were occasionally more accurate but less likely to respond.“A child’s temperament, especially their shyness, could strongly impact how they will do in language tasks,” said Kucker. “When children are given assessments to evaluate their language abilities, clinicians and teachers should take into account the child’s shyness level, perhaps using tasks that are less burdensome for them, such as pointing tasks instead of verbal ones.”Kucker believes acknowledging the impact of shyness will help professionals ensure language assessments are more effective and provide a more comprehensive understanding of a child’s linguistic development. Moving forward, she and her team plan to explore the performance of shy and less-shy children on standardized language assessments.8．What is the main purpose of the research conducted by Sarah Kucker?A．To develop new language assessment tasks for young children.B．To compare the intelligence levels of shy and less-shy children.C．To identify the root causes of shyness in children under four years old.D．To understand shyness impact on kids’ performance in language assessments.9．Why did the researcher ask parents to answer a questionnaire?A．To assign tasks accordingly.B．To judge the children’s ability.C．To assess the children’s shyness.D．To know about the children’s strength. 10．What can be inferred about the pointing task?A．It was the hardest task.B．It favoured shy children.C．It was too easy for children.D．It was unaffected by shyness.11．Which field can the findings be applied to?A．Language learning.B．Character building.C．Behaviour management.D．Task designing.Have you ever worried that you might smell bad? Well, you do have a smell, but not in the way you think. The human body releases hundreds of chemical compounds into the air every day, and these compounds reveal much more than just our health habits; they can also indicate our health situations.In 1971, chemist Linus Pauling identified 250 different gaseous chemicals in our breath, known as VOCs. These VOCs originate from the body’s metabolic (新陈代谢) processes and are excreted (排泄) through skin glands. While sweat contributes to these VOCs, it only accounts fora small portion of them.VOCs can reveal a lot about our health. For example, a sweet-smelling breath could be a sign of diabetes. Besides breath, VOCs are also released from our skin, and feces (粪便). A notable case involved Joy Milne, who noticed a change in her husband’s smell 12 years before he was diagnosed with Parkinson’s disease. Known as “the woman who can smell Parkinson’s,” Joy has been using her keen sense of smell to help scientists develop a simple swab (拭子) test to diagnose the illnesses.Animals with advanced sense of smell, like dogs, have demonstrated they can detect various types of cancer in humans. Although these smells are often undetectable to the human nose, they provide evidence that our bodies emit different smells when something is wrong.The relationship between VOCs and our health is still being studied. Studies have already shown that they can predict a person’s age within a few years based on their skin VOC profile. In one interview, Professor Morin stated, “We are at a relatively early stage in this research area, but we have already distinguished males from females based on the acidity of skin VOCs. We believe skin VOCs can reveal aspects of who we are, such as nutrition, health and stress. These signatures likely contain markers that can be used to diagnose disease.”So, who knows — maybe one day we will be able to detect diseases simply by breathing into a device.12．What do we know about the VOCs according to the text?A．Skin VOCs reveal more about our health conditions.B．The VOCs mostly come from sweat.C．VOCs only released from our skin can indicate health status.D．Our body’s metabolic processes are the source of VOCs.13．Why does the author mention animals in Paragraph 4?A．To show the amazing wisdom of animals.B．To stress we must depend on pets more to detect cancer.C．To explain VOCs have the capability to cure cancers.D．To highlight VOCs’ potential as diagnostic markers.14．What future technology might arise from the understanding of VOCs?A．Equipment that can analyze VOCs to diagnose diseases.B．Devices that can breathe out disease-causing VOCs.C．Advanced facilities that can use VOCs to cure diseases.D．Personalized perfumes that can mask disease-related VOCs.15．Which of the following is the best title for the text?A．Morin’s Contributions to VOCsB．The Function of Sweat in Our HealthC．Detecting Diseases Through Body SmellsD．Body Smell Resulting in DiseasesOnce upon a time, sewing and mending (缝补) clothes was common. At some point in the last few decades, though, it became something of a lost art. 16 Schools stopped offering home economics classes, technology boomed and fast fashion became increasingly popular. All of a sudden, it’s more inconvenient to fix something than it is to buy something new.But all hope is not lost. 17 On one of the most pleasant corners of the Internet, you’ll find lots of videos showcasing everything from visible mending to beginner sewing journeys.18 Mending is a great way to reject consumerism. As any eco-expert will tell you, the best thing you can do is buy less to begin with. That means shopping for quality items that will stand the test of time, but also learning a few key skills so you can repair those items as needed rather than sentencing them to life in an already-overflowing landfill. It’s also helpful to customize (改制) secondhand items which might not be exactly the right size or a little out of date. 19 Beyond the functional benefits, mending is about using what you have, embracing imperfections, fixing what’s broken, and rejecting the idea that newer is better. The other aspect of mending is mindfulness. You focus on the task at hand and use your creativity to make your clothes unique. It’s meditative (冥想的), slow work. 20 And an added bonus: It’s sustainable.If you are interested in sewing and mending, it is the perfect time to learn the new skill, which can especially have a positive impact on the world.A．Why should you learn to mend?B．This is a means of making a living.C．It’s productive, and deeply satisfying.D．Purchasing secondhand clothes is a good choice.E．Why have people stopped mending their clothing?F．This way, you may find yourself upcycling pieces into ones that suit you.G．In the past few years, there’s been growing interest in slow fashion — sewing and mending.二、完形填空Over the weekend, a flood damaged houses, roads, and bridges, leaving many people nowhere to go. The powerful flood damaged Hagan’s 21 , leaving him and his wife22 from the community (社区). He turned to social media but never imagined he would23 a call from his grandson’s coach Ryan Jesop. “The Hagans have done so much for this area, so it was an easy decision to 24 ,” Jesop said.The Switzerland County football coach drew up a plan telling his team to build a new bridge in place of the old 25 one. Hagan received a(n) 26 that a team would be at his house Monday at 9 a. m. to work. “People I’d never seen before were walking down my driveway to help us,” Hagan said. “It was 27 and brought tears to my eyes.”28 , the steel frame base structure (钢架基础结构) of the bridge wasn’t damaged by the flooding. Dozens of people went to the bridge and 29 the old one plank (木板) by plank. Then the team built it back up by 30 an assembly line (流水线). “The 31 of our team is to help them through teamwork,” student Linebacker Gabriel Rose said. The team32 the project in only a few hours. “They were here at nine o’clock, and I looked at my33 when it was done and it was 11:45 a.m.,” Hagan said. The Hagans now reconnected with their 34 thanks to their grandson’s football team. As for Coach Jesop, he is chalking it up as the biggest 35 of the season.21．A．bridge B．room C．land D．garden 22．A．defended B．excused C．discouraged D．separated 23．A．give B．receive C．pay D．remember 24．A．shift B．cease C．help D．check 25．A．broken B．abandoned C．splendid D．traditional26．A．order B．message C．report D．opinion 27．A．touching B．shocking C．confusing D．frightening 28．A．Suddenly B．Fundamentally C．Fortunately D．Certainly 29．A．took apart B．took over C．took up D．took off 30．A．preserving B．creating C．transforming D．recording 31．A．mission B．career C．question D．travel 32．A．integrated B．completed C．designed D．examined 33．A．window B．sky C．tree D．watch 34．A．fans B．neighbourhood C．investors D．firm35．A．win B．leadership C．qualification D．wish三、语法填空阅读下面短文，在空白处填入1个适当的单词或括号内单词的正确形式。
反相高效液相色谱法测定人血清中奥卡西平活性代谢产物的浓度目的建立反相高效液相色谱法测定人血清中奥卡西平（OXC）活性代谢产物MHD的浓度。
方法收集血清样品经甲醇沉淀蛋白后，采用InertSustain C18（5 μm，4.6×150 mm）色谱柱，流动相为甲醇-水（35：65），流速：0.8 mL/min，检测波长：210 nm，柱温：40℃，进样体积：20 μL。
结果血清中内源性物质对样品测定无干扰，MHD 在 4.8～38.4 μg/mL线性关系良好，回归方程为：A=13968.3C-13730.7，r=0.9990。
MHD的低、中、高3种浓度平均回收率均>95%，日内、间RSD 均95%，and intra-and inter-day RSDs were 95%，日内、日间RSD均35 μg/mL占0。
结果显示OXC在按常规剂量给药的情况下，存在部分患者血药浓度在有效浓度范围外，因此，需要在血药浓度监测下调整给药剂量，本方法能够满足临床血药浓度监测，也能用于患者过量服药情况下的中毒药物浓度监测，从而为患者制定个体化用药方案。
3 讨论从奥卡西平的药动学特征来看，口服OXC后，其活性代谢产物MHD一般在2～3 d内达到稳态血药浓度。
本文对癫痫患者口服OXC片后进行TDM，在给药前采集血样测定人血清中MHD稳态谷浓度水平。
MHD在人血清中的血药浓度测定方法已有文献报道，通常采用LC-MS/MS法[7]和HPLC法[8-16]。
LC-MS/MS专属性强、灵敏度高，但由于成本昂贵，不适用于常规检测。
目前国内关于MHD药物浓度测定的HPLC法大多采用内标法进行测定[9-11，16]，操作较为繁琐，本文采用外标法进行测定，实验结果表明该方法简便快捷，也能准确地测定MHD的血药浓度。
MHD结构中有两个苯环，具有明显的紫外吸收。
本实验在200～360 nm的波长范围内进行紫外扫描，发现检测波长为210 nm时，基线平稳，吸收值较大，灵敏度较高，因此选取210 nm作为检测波长。
Carbamazepine and Its Metabolites in Wastewater and in Biosolids in a Municipal Wastewater Treatment PlantX I U-S H E N G M I A O,J I A N-J U N Y A N G,A N D C H R I S D.M E T C A L F E*Water Quality Centre,Trent University,Peterborough, Ontario K9J7B8,CanadaPharmaceutically active compounds(PhACs)are discharged into the environment from domestic wastewater treatment plants(WWTPs).In this study,we determined the distribution of the anti-epileptic drug,carbamazepine (CBZ),and its major metabolites and caffeine in both aqueous and solid phases through different treatment processes of a WWTP.A method was developed to extract samples of biosolids using pressurized liquid extraction (PLE),coupled with cleanup of extracts using solid-phase extraction.Samples of biosolids and wastewater were analyzed for caffeine and CBZ and five of its metabolites,10,-11-dihydro-10,11-epoxycarbamazepine(CBZ-EP),11-dihydro-10,11-epoxycarbamazepine(CBZ-DiOH),2-hydroxycar-bamazepine(CBZ-2OH),3-hydroxycarbamazepine(CBZ-3OH),and10,11-dihydro-10-hydroxycarbamazepine(CBZ-10OH).The analytes were quantified using liquid chromatography-electrospray ionization tandem mass spectrometry.The recoveries of the analytes were82.1-91.3%from raw biosolids and80.1-92.4%from treated biosolids,and the limits of detection were0.06-0.50and0.06-0.40µg/kg on a wet weight basis for raw and treated biosolids,respectively.The behavior of carbamazepine and its metabolites,together with caffeine as a marker of domestic inputs,was investigated in the WWTP for the City of Peterborough,ON,Canada,which utilizes secondary sewage treatment technologies.CBZ,CBZ-2OH,CBZ-3OH,and CBZ-DiOH were detected at concentrations of 69.6,1.9,1.6,and7.5µg/kg(dry weight),respectively,in untreated biosolids and at concentrations of258.1,3.4,4.3, and15.4µg/kg(dry weight),respectively,in treated biosolids.However,CBZ-EP and CBZ-10OH were not detected in any of the biosolid samples.CBZ and its five metabolites were detected in all wastewater samples collected from four different stages of treatment.The results showed that29%of the carbamazepine was removed from the aqueous phase during treatment in the WWTP, while the metabolites were not effectively removed. Concentrations of caffeine were reduced by99.9%in the aqueous phase,which appeared to be due primarily to degradation.Caffeine was also detected at concentrations of165.8and7.6µg/kg(dry weight)in raw and treated biosolids,respectively.Because of differences in hydrophobicity,CBZ is the primary analyte in biosolids, while CBZ-DiOH is the primary analyte in the aqueous phase of the wastewater.A mass balance calculation showed that the majority of CBZ and its metabolites exist in the aqueous phase(i.e.,wastewater),rather than in the biosolids, 78g of CBZ and its metabolites enters the Peterborough WWTP daily,and91g is discharged from the WWTP daily in the combined suspended solids and aqueous phasesof the wastewater.The calculated daily inputs into the WWTP are somewhat less than the inputs of192g estimated from Canadian annual sales data for CBZ.IntroductionPharmaceutically active compounds(PhACs)are an emerging environmental issue,due to their presence in the aquatic environment and potential for impacts on wildlife and humans(1,2).Some metabolites of pharmaceuticals are still bioactive,and they may have high stability and mobility in the environment.Therefore,the fate of metabolites is a very important component of assessing the environmental risks associated with the release of PhACs.Municipal wastewater treatment plants(WWTP)are one of the major sources of PhACs in the environment(3,4).Many chemical,physical, and biological factors may affect the fate of PhACs in WWTPs, including adsorption/desorption on biosolids(i.e.,sludge), pH,the ionic strength of the sewage,microbial decomposition rates,and the physical and chemical properties of the PhACs (e.g.,polarity,photostability,volatility,etc.).Hydrophilic compounds that are resistant to degradation may remain dissolved in the aqueous phase of the WWTP effluent,or more hydrophobic substance may bind to the biosolids.Thus, these compounds may enter the environment through the discharge of WWTP effluents into receiving waters or they may enter the environment in association with biosolids that are deposited in landfills or spread onto agricultural land for soil amendment.Pharmaceutical compounds discharged into surface water have the potential to contaminate sources of drinking water(5,6).In addition,some pharmaceuticals have been detected in groundwater(7-9).Since WWTPs provide the first and perhaps most im-portant opportunity for removing pharmaceuticals that are destined for discharge into the environment,it is important to characterize the fate of pharmaceuticals during the treatment of domestic wastewater.The most important process that governs whether pharmaceuticals will primarily enter the aquatic or terrestrial environments is whether these compounds partition from aqueous sewage into sludge.Some studies have been conducted on the distribution of PhACs within sewage in WWTPs(10-12),but there have been only few studies on PhACs and their metabolites in both sewage and sludge.In this study,we analyzed carbamazepine(CBZ)and its major metabolites in both aqueous and biosolid phases of a municipal WWTP.CBZ is an important drug for the treatment of epilepsy,as well as for various psychotherapy applications.In Canada,approximately28tons of carbam-azepine was sold as prescriptions in2001(13).Studies in Europe and North America have shown that CBZ is one of the most frequently detected pharmaceuticals in WWTP effluents and in river water(3,8,14,15).We previously detected CBZ and five of its metabolites in the effluents of WWTPs in Canada and CBZ and one of these metabolites, 10,11-dihydro-10,11-dihydroxycarbamazepine(CBZ-DiOH), in surface water(16).CBZ undergoes extensive hepatic metabolism by the cytochrome P450(CYP)system(17,18).Thirty-three me-*Corresponding author phone:(705)748-1011,×7272;fax:(705)-748-1569;e-mail:cmetcalfe@trentu.ca.10.1021/es050261e CCC:$30.25 2005American Chemical Society VOL.39,NO.19,2005/ENVIRONMENTAL SCIENCE&TECHNOLOGY97469 Published on Web09/07/2005tabolites of CBZhave been identified from human and raturine(19).The main metabolic pathway for CBZ is oxidation to10,11-dihydro-10,11-epoxycarbamazepine(CBZ-EP),then hydration to CBZ-DiOH and conjugation of CBZ-DiOH with glucuronide.The hydrolysis of CBZ-EP to CBZ-DiOH is catalyzed by microsomal epoxide hydrolase(20).The me-tabolism of CBZ to CBZ-EP appears to be catalyzed by CYP3A4 and CYP2C8.Lesser pathways include oxidation to2-hy-droxycarbamazepine(CBZ-2OH)and3-hydroxycarbam-azepine(CBZ-3OH),which appear to be catalyzed by CYP1A2, as well as oxidation to10,11-dihydro-10-hydroxycarbam-azepine(CBZ-10OH).The most important metabolites are CBZ-DiOH and,to a lesser extent,CBZ-EP.The latter compound has been shown to possess similar anti-epileptic properties to CBZ,and it may cause neurotoxic effects(21,22).In some cases,clinical toxicities parallel CBZ-EP concentration(23).Despite being chemically stable under physiological conditions,CBZ-EP is converted to the CBZ-DiOH metabolite by epoxide hydrolase. Bernus et al.(24)investigated the metabolism of CBZ in women during pregnancy and found that CBZ,CBZ-EP,CBZ-DiOH,CBZ-acridan,CBZ-2OH,and CBZ-3OH accounted for 0.5,2.1,34.6,3.2,2.3,and3.7%of total concentrations in urine samples,respectively.The CBZ-DiOH metabolite is not pharmaceutically active.Caffeine has been used as a chemical marker for human excretory products discharged in domestic wastewater(14, 25,26).Canadian annual consumption of caffeine is close to 2.2×103tons a year,or240mg per person per day(27), which is largely excreted in urine and transported into domestic sewage.We monitored the concentrations of CBZ and its major metabolites and caffeine in the aqueous phase of wastewater and in biosolids at various stages of treatment in the WWTP for the City of Peterborough,ON,Canada.To conduct this study,it was necessary to develop methods for the analysis of the CBZ and metabolites in biosolids.We developed a method for extraction of analytes using pressurized liquid extraction(PLE)and a method for cleanup of the extracts using solid-phase extraction(SPE)cartridges.Extracts were then analyzed using liquid chromatography-electrospray tandem mass spectrometry(LC-ES-MS/MS). Experimental ProceduresChemicals.The formulas,abbreviations used in figures and tables,molecular weights,and log K ow values for the analytes are summarized in Table1.CBZ,CBZ-EP,CBZ-DiOH,CBZ-2OH,CBZ-3OH,and CBZ-10OH were provided by Novartis Pharma AG(Basel,Switzerland).Caffeine(1,3,7-trimethyl-xanthine)and ammonium acetate(98%)were purchased from Sigma-Aldrich Canada(Oakville,ON,Canada).A surrogate standard of caffeine(trimethyl-13C3,99%)was purchased from Cambridge Isotope Laboratories(Andover, MA).Acetonitrile and methanol were purchased from Caledon Laboratories(Georgetown,ON,Canada).Formic acid(90%)and HPLC grade water were purchased from EM Science Industries(Gibbstown,NJ).Hydromatrix was pur-chased from Varian Canada(Mississauga,ON,Canada).Sampling.The WWTP investigated in the small city of Peterborough,ON,Canada employs secondary(i.e.,activated sludge)sewage treatment technologies(Scheme1).Second-TABLE1.Molecular Structures,Abbreviations,Formulas,Molecular Weights,and Log K ow of Carbamazepine and Its Metabolites and Caffeinea Chemical Abstracts Service registry number.b Molecular weight(MW)was calculated for the lowest isotopomer.c Ref32.d Values of log K ow of carbamazepine and its metabolites were calculated with ACD/log P.e Ref34.ary sewage treatment is the most common technology used in WWTPs in Canada.The Peterborough WWTP serves a population of about75000people.Its design average flow capacity is60000m3/day,and its average handling flow is 46000m3/day(77%of its design capacity).The influent flow rate consists of about25%industrial wastewater and75% domestic sewage.The wastewater entering the WWTP is first treated mechanically using grit removal and screening and goes to the primary clarifier.The primary effluent is directed to an activated sludge system for biological treatment in the aeration tank and then goes to the second clarifier.Full aeration is provided for complete nitrification in the aeration tank.After settling in the secondary clarifier,the wastewater is disinfected by UV irradiation at30mW s-1cm-2.Following irradiation with UV,the treated effluent is discharged to the Otonabee River.The hydraulic retention time for the wastewater in the WWTP is12-18h.As for the biosolids,some activated sludge from the secondary clarifier is returned to the inlet of the primary clarifier,and the remainder goes to the digester(anaerobic) and is combined with primary sludge(Scheme1).The biosolid treatment process prior to input into the digester is operated at ambient temperatures with a retention time of4-6days, which varies with wastewater flow and treatment conditions. In the digester,the biosolids are stabilized by thermal treatment at37°C for approximately30days.The treated biosolids are then ready to be shipped from the WWTP for application to agricultural fields.Samples of wastewater were collected as flow proportional composites using automated samplers that collected defined volumes every hour over a24h period.Samples of biosolids were collected as grab samples.On April28,2003,samples were collected of untreated wastewater(site A),treated wastewater after UV(site D),untreated biosolids(site E), and treated biosolids(site F),according to the sites shown in Scheme1.On July14,2003,composite samples were collected of untreated wastewater(site A),primary wastewater (site B),treated wastewater before UV treatment(site C), and treated wastewater after UV treatment(site D).After collection,the wastewater samples were filtered through0.45µm glass filters and immediately transported to the laboratory,where they were stored at4°C in a cold room until preparation for analysis,which generally occurred within24h of collection.The biosolid samples were concentrated by centrifugation at2500rpm for5min at room temperature and frozen in amber jars until analysis.The moisture content of the biosolids was expressed as the ratio of the mass of water to the dry weight of the biosolids sample, after drying in an oven at a temperature of105°C for24h.Preparation of Wastewater and Biosolid Samples. Thawed samples of centrifuged biosolids(10g)were extracted by PLE using an ASE300accelerated solvent extractor (Dionex,Sunnyvale,CA)equipped with34mL stainless extraction cells.To dry the sample,reduce particle clumping and solvent channeling in the extraction cell,and reduce the void volume,Hydromatrix was mixed with biosolids.Hy-dromatrix is a specially cleaned and sieved diatomaceous earth and is capable of adsorbing and retaining up to twice its weight of aqueous media(i.e.,aqueous capacity is2mL water per g of Hydromatrix).The amount of Hydromatrix added(2-10g)depended on the water content of the sludge sample.The extraction procedure was optimized for extraction temperature,extraction time,and the extraction solvent using sludge samples spiked with the analytes.For all PLE experiments,a fixed extraction pressure of1500psi was used. The other optimized PLE conditions were prefill method: solvents,acetone/water(3:7);equilibration,5min;static time, 5min;flush volume,60%;purge time,60s;static cycles,3; and temperature,80°C.The flush volume amounted to100% of the extraction cell volume,and the total solvent use was approximately90mL.After PLE extraction,the extract was poured into a250 mL boiling flask,and the acetone was evaporated using a rotary evaporator at40°C.After evaporation,the remaining aqueous matrix was diluted with100mL of HPLC water.This matrix was cleaned up by SPE using HLB Oasis extraction cartridges(Waters,Milford,MA).SPE cartridges were con-ditioned,and the sample extraction was conducted as previously described for the extraction of aqueous samples (16).A volume of0.5L of wastewater was extracted using the same SPE extraction protocol that was used for cleanup of extracts from biosolids.Analysis.Mass spectrometry was performed using a Quattro LC tandem quadrupole mass spectrometer(Micro-mass,Manchester,UK)equipped with a Z-Spray electrospray ionization source.Analyte separations were conducted with an Alliance2695liquid chromatograph(Waters,Milford,MA) with a Genesis C8column(150mm×2.1mm i.d.,3µm) purchased from Jones Chromatography,Hengoed,Mid Glamorgan,UK.The conditions for LC-ES-MS/MS in selected reaction monitoring(SRM)mode for CBZ and its metabolites have been reported previously(16).SRM chan-nels of m/z195>138and198>140were used for analysis of caffeine and a13C3-labeled caffeine surrogate,respectively.Organic coextractives are responsible for matrix effects with electrospray ionization mass spectrometry,especially for the determination of trace contaminants in environmental samples.To compensate for matrix effects,a surrogate of 13C3-labeled caffeine was used as an internal standard to quantify caffeine.At the time of this study,there was no stable isotope surrogate for CBZ commercially available. Therefore,for the analysis of CBZ and its metabolites,the analytes were quantified using calibration by standard additions,as reported previously(16).Briefly,this method involves spiking five subsamples with a dilution series of the analytes,then constructing a calibration curve for the analytesSCHEME1.Flow Chart of the Peterborough WWTP,Showing the Sampling Sites(A-F)within the sample matrix.Three other unspiked subsamples were analyzed at the same time to yield triplicate analyses of each sample.Results and DiscussionEvaluation of Sample Preparation Methods for Biosolid Samples.Extraction efficiency by PLE is mainly governed by the solubility of the analytes in the extraction solvent.Because organic solvents cannot be passed through the SPE following PLE extraction,acetone was chosen as the extraction solvent since it can be easily removed by evaporation at moderate temperatures(i.e.,40°C)prior to the SPE cleanup step. Different proportions of acetone and water were investigated for maximum extraction efficiency by PLE.A high percentage of acetone caused more organic coextractives to be extracted and resulted in clogging of the SPE cartridge and complex chromatograms.Extraction efficiencies for the analytes were poor if the solvent mixture contained more than80%water. A3:7mixture of acetone and water optimally extracted CBZ and its metabolites and caffeine.However,temperature also influences PLE extraction efficiency.Higher temperatures decrease the viscosity of water,thus allowing better penetra-tion of the sample matrix,but higher temperatures may increase the amounts of unwanted coextractives and result in degradation of thermally labile analytes.A solvent tem-perature of80°C was found to be optimal for extraction of all analytes.However,failures in PLE were experienced as a result of the high back-pressure when extracting wet biosolids. Therefore,Hydromatrix was mixed with biosolid samples to absorb water and improve permeation of the sample matrix by the extraction solvent.To evaluate the extraction method for samples of biosolids, samples of raw and treated biosolids(wet)were spiked with the analytes.After the biosolid samples were allowed to stabilize for2h,they were extracted using the optimized PLE method.Table2lists the percent recoveries of the analytes, which ranged from82.1to91.3%in raw biosolids and from 80.1to92.4%in treated biosolids,with standard deviations of3.6-8.4%.The limits of detection(LODs)and limits of quantification(LOQs)of the analytes for combined PLE, followed by SPE cleanup,were determined by spiking sludge samples with the analytes(Table2).The LOD and LOQ were defined as concentrations in a sample matrix resulting in peak areas with signal-to-noise ratios(S/N)of3and10, respectively.The mean water contents of raw and treated biosolids samples in this study were84.4and81.7%, respectively.Distribution of CBZ and Its Metabolites.Previous studies have shown that CBZ is relatively persistent within WWTPs (3,4).Analytical data for wastewater and biosolids collected from the Peterborough WWTP in April2003(Table3)are generally consistent with these previous studies.The mean concentration of CBZ declined from356ng/L in the untreated wastewater to251ng/L(29%decline)in the treated waste-water.The metabolite,CBZ-DiOH,was the predominant analyte in the aqueous phase(Table3),which is consistent with our earlier studies(16).No loss of the metabolites of CBZ was observed in the aqueous phase(Table3).Indeed, the concentrations of CBZ-2OH and CBZ-DiOH increased significantly in the treated wastewater relative to concentra-tions in the untreated wastewater.The hydroxylated me-tabolites of CBZ occur primarily in conjugated forms in human biological fluids(28),and these conjugated metabo-lites could have been transformed to the free form by microbial activity during treatment,as was described previ-ously for estrogens(29).More work is required to determine the mechanism involved in this observed response.Note that the samples of wastewater represent composite samples collected over a24h period,so these data should integrate daily posite sampling over several days(e.g., 4-5days)would have integrated variations over a longer period of time within the WWTP,but this sampling scheme was rejected because of concerns over the potential for degradation of some of the analytes in the wastewater matrix over a long-term sampling period.In the biosolid samples collected in April2003,only CBZ and three of the metabolites,CBZ-2OH,CBZ-3OH,and CBZ-DiOH,were detected,with CBZ as the predominant analyte (Table3).The metabolite that was dominant in the waste-water,CBZ-DiOH,did not partition into the biosolids to high concentrations due to its hydrophilicity.Two of the me-tabolites that were detected in the aqueous phase,CBZ-EP and CBZ-10OH,were not detected in the biosolid samples. Many PhACs have relatively low log K ow values,relative to legacy contaminants,such as PCBs and polynuclear aromatic hydrocarbons,which have log K ow values between4.5and8.5(30).Compounds with log K ow<2.5are assumed to havea low potential for adsorption onto particulates(31).As shown in Table1,the metabolites of CBZ have log K ow values between 0.13and2.41,in comparison to the log K ow for CBZ of2.67 (or2.25)(32).The concentrations of CBZ and metabolites increased on a dry weight basis between untreated and treated biosolids(Table3).This may be due to the different composition of untreated and treated biosolids,which show different adsorption behaviors.Another explanation may be the recycling of excess return activated sludge back to the untreated sludge,leaving behind the more highly concen-trated biosolid substrate as the treated material.In any event, more studies are required to determine the mechanisms for this observation.TABLE2.Mean Recoveries with Standard Deviations andLimits of Detection(LODs)and Limits of Quantification(LOQs)of CBZ and Its Metabolites and Caffeine Spiked into Samplesof Raw and Treated Biosolids(µg/kg,Wet Weight)araw biosolids treated biosolidsanalyte recovery(%)LOD LOQ recovery(%)LOD LOQCBZ91.3(5.80.150.5092.4(3.70.170.58CBZ-EP86.1(8.40.060.2287.7(4.50.070.23CBZ-DiOH83.6(4.40.110.3282.8(8.10.100.34CBZ-2OH84.0(6.90.080.2689.1(3.60.070.22CBZ-3OH83.8(7.90.070.2280.1(6.50.060.20CBZ-10OH88.4(4.80.100.3490.4(5.10.080.28caffeine82.1(5.60.50 1.7083.2(6.10.40 1.35a Recoveries are the average of three determinations at spikedconcentrations of10µg/kg(wet weight).TABLE3.Mean((Standard Deviation in Brackets)of the Concentrations of CBZ and Its Metabolites in Wastewater(ng/L)and in Biosolids(µg/kg Dry Weight)at Various Stages of Treatment in the Peterborough WWTP asample and units CBZ CBZ-EP CBZ-2OH CBZ-3OH CBZ-10OH CBZ-DiOH untreated wastewater(ng/L)356.1((5.8)39.2((1.2)59.0((2.1)55.4((6.1)22.2((2.5)1001.2((12.5) treated wastewater251.0((6.3)19.1((1.5)70.4((2.3)69.2((3.1)32.5((2.4)1081.2((13.0) untreated biosolids(µg/kg dry weight)69.6((2.2)n.d. 1.9((1.1) 1.6((0.8)n.d.7.5((0.7) treated biosolids258.1((4.7)n.d. 3.4((0.9) 4.3((0.9)n.d.15.4((1.3)a All samples were collected on April28,2003and were analyzed in triplicate.n.d.)not detected.To more fully investigate the fate of CBZ and its me-tabolites in the aqueous phase of the wastewater in the Peterborough WWTP,samples were collected in July2003as untreated wastewater,primary wastewater(after the primary clarifier),and treated wastewater before and after UV disinfection.Figure1illustrates the profile of CBZ and its metabolites in the aqueous phase of sewage at different stages of treatment.Once again,CBZ and all metabolites were detected in the wastewater samples,and CBZ-DiOH was the predominant analyte.The concentration of CBZ in the aqueous phase of the wastewater declined from651ng/L in the untreated wastewater to353ng/L(46%decline)in the primary sewage,indicating effective removal of this com-pound from the aqueous phase by the primary clarifier. However,the concentration of CBZ in the treated effluent (after UV)subsequently increased to a final concentration of463ng/L.Removal over the total treatment process was 29%,which is higher than the removal rates of less than10% reported for WWTPs in Germany(3).Further investigations should be conducted to determine the specific mechanisms for removal of CBZ within the WWTP.Figure1indicates that the concentrations of CBZ,CBZ-DiOH,and CBZ-10OH increased significantly after UV disinfection,in comparison to the samples collected before UV disinfection.In particular,the concentration of CBZ-10OH increased from843ng/L in the treated sewage before UV to1065ng/L in the sewage after UV(Figure1).We have previously observed this response to UV treatment,specif-ically,an increase in the concentrations of synthetic musks after UV treatment in the Peterborough WWTP(33).It is possible that UV irradiation mediates the conversion of the conjugated forms of the hydroxyl metabolites of CBZ to the free form and/or modifies the dissolved organic matrix in the treated wastewater so that analytes are released from the bound to the dissolved phase.Obviously,more work is required to elucidate the mechanism involved in this response,including whether the level of UV irradiation is sufficient to alter the wastewater matrix.Caffeine was used in this study as a marker of human excretory inputs into the domestic sewage.In samples collected in April2003,the mean concentration of caffeine in the untreated wastewater was63.2µg/L,which is far higher than the ng/L concentrations of CBZ and metabolites in the treated wastewater.Approximately99.9%of the caffeine was removed from the aqueous phase by the treatment process,as the concentration of caffeine was0.068µg/L(i.e., 68ng/L)in the treated wastewater.This observation is consistent with previous data that show high rates of elimination of caffeine in WWTPs(25,26).Despite caffeine being hydrophilic(34),this compound was detected at concentrations of165.8and7.6µg/kg(dry weight)in raw and treated biosolids,respectively,for a95.4%rate of elimination of caffeine from biosolids.These data for caffeine contrast to the data for CBZ and its metabolites,which appear to be relatively resistant to degradation in WWTPs.Degrada-tion appears to be a major mechanism for the elimination of caffeine from municipal wastewater.Mass Balance of CBZ and Metabolites.To evaluate the fate of CBZ and its metabolites in the sewage in the Peterborough WWTP,a mass balance approach was used to evaluate the distribution of the analytes in the aqueous and suspended solids phases of the wastewater.We assumed that the concentrations of CBZ and its metabolites in the suspended solid phase of the raw and treated wastewater were approximately equal to their corresponding concentra-tions in raw and treated biosolids,respectively(Table3). Related data for mass balance calculations such as flow rates and the total suspended solid content of the wastewater were collected at the Peterborough WWTP during the sampling period and are listed in Table4.The daily inputs and outputs of the analytes in the aqueous and solids phases of the WWTP were calculated using eqs1and2,respectively.For the aqueous phasewhere M i is the daily input or output of analyte i in the aqueous phase,g;C i is the concentration of analyte i in raw or treated wastewater(ng/L);and Q j is the flow of raw sewage or treated wastewater(m3/day).For the suspended solid phasewhere M i is the daily input or output of analyte i in the suspended solid phase(g),C i is the concentration of analyte i in the raw or treated biosolids(ng/kg dry weight),Q j is the flow of raw or treated wastewater(m3/day),and S j is the suspended solid content in raw or treated wastewater (mg/L).Table5presents the results of the mass balance calcula-tions for CBZ and its metabolites in the aqueous and suspended solid phases of the wastewater in the Peterborough WWTP.The results show that CBZ and CBZ-DiOH were the predominant compounds in the wastewater.The majority of CBZ and metabolites exists in the aqueous phase of the wastewater,and the proportion of CBZ in the suspended solid portion of the wastewater only accounted for0.45and 0.15%of the total amount(aqueous+suspended solids)in the raw and treated wastewater,respectively.The daily input and output of CBZ and its metabolites in the sewage of the Peterborough WWTP was79and91g,respectively.It is acknowledged that caution must be used in the interpretation of these data since the mass balances are based on single24 h composite samples for wastewater and grab samples of biosolids.FIGURE1.Mean concentrations(ng/L)of CBZ and its metabolites in the aqueous phase of wastewater through different stages of treatment in the Peterborough WWTP.Samples were collected on July14,2003,and sampling sites A-D are marked in Scheme1. Samples were analyzed in triplicate.TABLE4.Related Data for Mass Balance Calculations in the Peterborough WWTP during the Sampling Period in April2003parameteruntreatedsewagetreatedsewageuntreatedsludgetreatedsludge flow(m3)5119659806suspended solids87mg/L8mg/L 3.9% 2.4% water content84.4%81.7%M i)C i Q j/1000000(1) M i)C i Q j S j/1000000000000(2)。
