Olanzapine

图1 个体化药物治疗的优势 一 什么是TDM？ 治疗药物监测（Therapeutic Drug Monitoring, TDM）是通过定量分析患者体液（主要是血液）中的药物浓度，结合药效学与药代动力学（PK/PD）原理，优化个体化给药方案的技术。 图2 血药浓度时间曲线 二 TDM核心检测技术 1.免疫分析法 原理：抗体-药物特异性结合，标记信号放大（如荧光、酶联）。 常用技术： 酶联免疫吸附试验（ELISA）：适用于大分子药物（如单抗）。 荧光偏振免疫分析（FPIA）（快速但易受代谢物干扰，如环孢素检测）。 优点：高通量、自动化（适合临床常规检测）。 缺点：可能受交叉反应干扰（如代谢物或结构类似物）。 2.色谱技术 高效液相色谱（HPLC）： 适用药物：多药联用监测（如抗精神病药组合）。 检测器：紫外（UV）、二极管阵列（DAD）或荧光检测器。 液相色谱-串联质谱（LC-MS/MS）（金标准）： 优势：高特异性、可同时检测多种药物（如抗生素、抗抑郁药）。 挑战：成本高、需复杂方法开发。 3.其他技术 气相色谱（GC-MS）：适用于挥发性药物（如丙戊酸）。 毛细管电泳（CE）：用于极性药物分离。 图3 研究过程示意图 三 质谱技术在TDM中的优势 1. 高特异性（抗干扰能力强） 精准区分目标药物与代谢物：免疫分析法可能因抗体交叉反应导致假阳性，而LC-MS/MS通过质量数（m/z）和碎片离子双重筛选，可明确区分目标药物与其代谢物。 减少内源性物质干扰：复杂生物样本（如血浆）中的蛋白质、脂类等对质谱信号影响极小。 2. 高灵敏度（检测限低） 可检测痕量药物（ng/mL甚至pg/mL级）：适用于低浓度药物（如抗抑郁药阿米替林）或小体积样本（如新生儿干血斑检测）。 扩展治疗窗狭窄药物的监测：例如：万古霉素（治疗窗10–20 μg/mL）的精准定量，避免毒性或治疗失败。 3. 多组分同步检测（高效性） 单次分析同时监测多种药物：例如：抗癫痫药（丙戊酸、卡马西平、苯妥英）联用时的浓度监测，避免多次采样。 兼容药物与内源性标志物联检：如同时检测免疫抑制剂（他克莫司）和肾功能标志物（肌酐）。 4. 方法开发灵活（广适用性） 无需抗体或特殊试剂：免疫分析法需针对每种药物开发抗体，而质谱只需优化色谱和质谱条件，适用于新药或罕见药（如新型抗肿瘤药）。 可检测非免疫原性药物：如小分子化学药（抗生素、抗真菌药）。 四 质谱技术在TDM中的应用 1.窄治疗窗药物的精准监测：万古霉素（10-20μg/mL）的峰/谷浓度监测，避免肾毒性。 2.多药联用监测：一针测多药，精神科患者同时监测奥氮平、舍曲林、丙戊酸。 3.游离药物浓度检测：低蛋白血症患者苯妥英监测，传统免疫分析法无法区分游离/结合型，LC-MS/MS检测检出限可低至ng/mL级别。 4.特殊人群TDM：新生儿干血斑万古霉素检测，仅需足跟血20μL，较传统方法减少80%样本量。 图4 TDM作用 五 总结 质谱技术通过高特异性、多组分分析和灵敏度提升，使TDM从“经验性用药”迈向“数据驱动精准用药”。目前质谱技术已成为临床诊断的“金标准”，尤其在复杂代谢分析、精准用药和罕见病诊断中不可替代。武汉生物样本库质谱检测服务平台在药物浓度监测及药代动力学中积累了丰富的经验，目前已检测上百种药物浓度检测，已建立了成熟的血药浓度监测技术方案并可进行方法验证，为药物临床研究提供助力。 来源：武汉生物样本库 END 扫码加小编微信，邀您进行业交流群 申请时请备注单位和姓名 往/期/回/顾 福利来啦！液相色谱串联质谱检测技术在临床上的应用有奖调研，诚邀参与！ 液相色谱串联质谱技术在治疗药物监测中的应用进展 血药浓度监测项目对不同科室在医院运营效益与临床价值分析 【质谱行业月报】国内首款质谱法肿瘤伴随诊断试剂盒获批上市！ 【行业标准】国产化检测仪器设备验证评价指南 液相色谱-质谱联用仪 原发性醛固酮增多症筛查：现状、挑战与对策 免责声明：本公众号的原创文章相关知识产权归临床质谱网所有，如需转载或引用文中内容（包括但不限于文字、图片等）请后台留言联系编者，获得授权后方可发布，未经授权严禁私自转载、删减、洗稿。本公众号的转载文章和观点仅代表原作者个人观点，不代表临床质谱网立场，所有内容仅供行业学习交流，不构成任何建议，无商业用途。我们尊重原创和版权，如有疏忽误引用您的版权内容，请及时联系我们处理！

Can Eli Lilly escape the boom-and-bust cycle that has long defined the pharma business? In January, Lilly CEO David Ricks was on stage with Nvidia CEO Jensen Huang. Ricks had recently (if briefly) joined the trillion-dollar club, a rarefied set of corporate chiefs whose companies have touched or exceeded that stratospheric valuation. Huang, a longtime member, wears it with the relaxation of his ever-present leather motorcycle jacket. Ricks, more often found in a sport jacket, is new to the club. To keep his spot, Ricks is trying to do what no pharma company has succeeded in. He needs to turn the windfall from Lilly’s massive success in weight loss into building a pipeline — and new technological approaches — that’s so broad, so forward-looking and so lucky, that he defies the gravitational pull of blockbuster patent expiries that reliably hauls down every high-flying drugmaker. On stage with Huang at an Nvidia event in San Francisco, Ricks called it achieving “exit velocity.” To do that, Lilly has undertaken a range of unusual ideas that could leave an impact on the biopharma ecosystem. While it’s busy building out its weight loss franchise with additional assets, it’s also partnering with Nvidia on a new AI-powered discovery lab , constructing an industry-leading supercomputer , offering an AI model-for-data swap to biotechs, leaning heavily into direct-to-patient sales , and partnering with the VC firm a16z on a new biotech fund . If it all works, Lilly could not only redefine the boundaries of drug company economics, but leave its stamp on the broader healthcare system itself. If it fails, the company — and Ricks — could end up redefining the meaning of “the bigger they are, the harder they fall.” “Lilly has a blend of exuberance and confidence of being the first trillion-dollar pharma combined with the paranoia and anxiety of sitting on what will become the biggest patent cliff in the industry’s history,”said Elliot Hershberg, who helps lead biotech investing at the VC firm Amplify Partners. He added that he views Lilly as playing on a different chessboard than the rest of the drugmaking giants. Ricks has brought an obsession with speed to Lilly, driven perhaps by his own memories of how quickly financial fortunes can turn. It has experienced two crushing patent cliffs, one with Prozac in 2001 and another with Zyprexa in 2011, that left the company as one of the industry’s least loved, until its recent success hauled it to new heights. Ricks called speed the most important element to improving R&D, therefore boosting Lilly’s future beyond today’s weight loss successes. The key patent for the main ingredient in Mounjaro and Zepbound won’t expire until 2036, but when that time comes, the loss could be enormous. “The challenge before us now is, how do we find another success cycle before that one runs out — hopefully a lot sooner than when it runs out,” Ricks told Huang, “and sort of get exit velocity. There’s really no major company in our industry that’s done that.” Ricks joined Lilly’s marketing department in 1996. He went from running the Canadian market to the Chinese market, eventually becoming CEO in 2017. In his first performance management review as the company’s leader, he was told he had an “overdeveloped sense of urgency.” That’s trickled down to the rest of the 50,000-employee company. “We have an impatient CEO,” Lilly’s chief information and digital officer Diogo Rau said in an interview, when asked about the collaboration with Nvidia. The companies are building a first-of-its-kind Bay Area laboratory that will physically co-locate scientists from both organizations to work on a range of AI moonshots in biopharma. The arrangement started with texts between Ricks and Huang last year. The goal is to open the Bay Area lab by the end of March, Rau said, a far faster speed than most big pharma companies typically build. Rau departed Apple to join Lilly in 2021. Some ex-Apple folks who followed him have told him they’re amazed by “how fast we move here,” he said. The speed means a lot of deals. Ricks said at his JPM presentation the business development team averaged a deal every nine days in 2025, totaling 39 on the year — far more than any other rival company. Many of these deals are a bit out-there compared to the standard, pipeline-stuffing tendency of large drugmakers. Some are higher-risk projects, like Verve’s cholesterol-lowering gene editing program or Ventyx’s inhibitors against NLRP3 , a target tied to aging-related diseases. Others, like the lab with Nvidia and bankrolling the a16z fund, are structured in ways even further divorced from the aim of bringing in specific drugs to boost revenue. Absent are any big, late-stage deals. Rau said the underlying driver is a willingness to “make bets on things we have high conviction on.” “We don’t necessarily require a brute financial case that might take three months to build,” Rau said. “We’ve learned from our past decisions that we regret more the things that we haven’t done or moved quickly on than the things we have done.” One of its first deals of 2026 was with Chai Discovery , an AI startup developing some leading protein design models. Its co-founders said the Lilly team was in its San Francisco office the week after it released details on its Chai-2 model last summer. Just a few months later, they became Chai’s first announced pharma partner. “They’ve just run through all sorts of walls to get the approvals they needed to make this happen really quickly,” Chai co-founder Jack Dent said in an interview. “That’s going to pay massive dividends for them. Other companies may want to take note.” Pharma peers, by comparison, seem like they’re treading water. Sanofi has struggled to answer what comes next after Dupixent, recently ousting Paul Hudson as CEO. Merck and Pfizer have made a flurry of expensive deals and major restructurings to brace for their own upcoming patent expiries on key drugs like Keytruda and Eliquis, which are expected before the end of this decade. Lilly has the chance to pursue a different fate. That will likely require hitting on some of the big-swinging ideas that could unlock huge patient populations, if successful. Those include a cholesterol-lowering gene editing program, large Alzheimer’s prevention studies, and non-opioid pain medications in the pipeline. “They’re incredibly ambitious, long-term thinkers,” a16z general partner Vineeta Agarwala said in an interview. “I do not think they are chasing patent cliffs.” It also hasn’t led to empire building, or a loss of discipline. Ricks says he has tried to keep headcount flat, and Lilly’s headcount grew by about 3,000 people, or 6%, over the last year, even as its revenue grew by 45% last year. He weighs in on all new hires and promotions above a certain level. “That makes me very unpopular,” he said on a recent podcast, an unusual, free-flowing two-hour-long conversation that sounded more like the loose, tech-cool Huang than the typical pharma CEO. “People are like, ‘How do I get this work done?’” The comparison extends to its market valuation, which makes Lilly look more like a Silicon Valley tech darling than a drugmaker. Lilly has kept a frenetic pace since the JP Morgan conference, when Ricks was on stage with Huang. They have given hints of what could be the next piece of the obesity story, in combination trials with some of its other drugs like Taltz that appear to boost efficacy in conditions like psoriasis. Outside of obesity, the first weeks of the year have included partnerships on gene editing and immunology, an acquisition of an in vivo CAR-T therapy, a sweeping R&D deal with a Chinese biotech powerhouse, and the announcement of a new Allentown, PA factory alongside Gov. Josh Shapiro. The unavoidable fate of pharma looms around every corner: Look no further than the downfall of its chief GLP-1 rival Novo Nordisk. In May, Lilly will celebrate its 150th anniversary. Next year, Ricks will celebrate his 10-year anniversary in the CEO job. For now, he and the company are on top. The real question is how long they can stay there.