{"id":6565,"date":"2025-09-09T15:16:19","date_gmt":"2025-09-09T15:16:19","guid":{"rendered":"https:\/\/www.waters.com\/blog\/?p=6565"},"modified":"2025-09-23T16:48:52","modified_gmt":"2025-09-23T16:48:52","slug":"how-advances-in-bioanalysis-drive-scientific-and-ethical-progress","status":"publish","type":"post","link":"https:\/\/www.waters.com\/blog\/how-advances-in-bioanalysis-drive-scientific-and-ethical-progress\/","title":{"rendered":"How Advances in Bioanalysis Drive Scientific and Ethical Progress"},"content":{"rendered":"<style>.wp-block-kadence-advancedheading.kt-adv-heading6565_937767-32, .wp-block-kadence-advancedheading.kt-adv-heading6565_937767-32[data-kb-block=\"kb-adv-heading6565_937767-32\"]{font-style:normal;}.wp-block-kadence-advancedheading.kt-adv-heading6565_937767-32 mark.kt-highlight, .wp-block-kadence-advancedheading.kt-adv-heading6565_937767-32[data-kb-block=\"kb-adv-heading6565_937767-32\"] mark.kt-highlight{font-style:normal;color:#f76a0c;-webkit-box-decoration-break:clone;box-decoration-break:clone;padding-top:0px;padding-right:0px;padding-bottom:0px;padding-left:0px;}.wp-block-kadence-advancedheading.kt-adv-heading6565_937767-32 img.kb-inline-image, .wp-block-kadence-advancedheading.kt-adv-heading6565_937767-32[data-kb-block=\"kb-adv-heading6565_937767-32\"] img.kb-inline-image{width:150px;vertical-align:baseline;}<\/style>\n<h2 class=\"kt-adv-heading6565_937767-32 wp-block-kadence-advancedheading\" data-kb-block=\"kb-adv-heading6565_937767-32\"><em>How Sygnature Discovery Supports the 3Rs with LC-MS\/MS<\/em><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n<style>.wp-block-kadence-advancedheading.kt-adv-heading6565_268ecc-2f, .wp-block-kadence-advancedheading.kt-adv-heading6565_268ecc-2f[data-kb-block=\"kb-adv-heading6565_268ecc-2f\"]{font-style:normal;}.wp-block-kadence-advancedheading.kt-adv-heading6565_268ecc-2f mark.kt-highlight, .wp-block-kadence-advancedheading.kt-adv-heading6565_268ecc-2f[data-kb-block=\"kb-adv-heading6565_268ecc-2f\"] mark.kt-highlight{font-style:normal;color:#f76a0c;-webkit-box-decoration-break:clone;box-decoration-break:clone;padding-top:0px;padding-right:0px;padding-bottom:0px;padding-left:0px;}.wp-block-kadence-advancedheading.kt-adv-heading6565_268ecc-2f img.kb-inline-image, .wp-block-kadence-advancedheading.kt-adv-heading6565_268ecc-2f[data-kb-block=\"kb-adv-heading6565_268ecc-2f\"] img.kb-inline-image{width:150px;vertical-align:baseline;}<\/style>\n<h2 class=\"kt-adv-heading6565_268ecc-2f wp-block-kadence-advancedheading\" data-kb-block=\"kb-adv-heading6565_268ecc-2f\">Scientific Precision and Ethical Innovation<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">In the world of drug discovery, researchers face a critical challenge: how do you generate high-quality, reproducible bioanalytical data while minimizing the ethical and logistical burden of using animals in testing?&nbsp; This is especially so with central nervous system (CNS) drug discovery, where obtaining biological samples from the CNS is not straightforward, resulting in multiple animals often being required to obtain the necessary data.<\/p>\n\n\n\n<div class=\"wp-block-group is-nowrap is-layout-flex wp-container-core-group-is-layout-8f761849 wp-block-group-is-layout-flex\">\n<p class=\"wp-block-paragraph\">This blog summarizes insights from a <a href=\"https:\/\/event.on24.com\/eventRegistration\/EventLobbyServlet?target=reg20.jsp&amp;eventid=4733147&amp;sessionid=1&amp;key=04DC16A251252FD1A99E4730FFBA7015&amp;groupId=5759526&amp;sourcepage=register&amp;partnerref=MoreFromLessBlog\">recent webinar<\/a> led by Dr. Stuart Best, Deputy Director of DMPK at <a href=\"https:\/\/www.sygnaturediscovery.com\/\">Sygnature Discovery<\/a>, on how the Sygnature team advances bioanalysis using LC-MS\/MS of low volume microdialysis samples, delivering robust and insightful CNS data with associated 3Rs benefits.<\/p>\n\n\n<style>.kb-image6565_a83b43-42.kb-image-is-ratio-size, .kb-image6565_a83b43-42 .kb-image-is-ratio-size{max-width:439px;width:100%;}.wp-block-kadence-column > .kt-inside-inner-col > .kb-image6565_a83b43-42.kb-image-is-ratio-size, .wp-block-kadence-column > .kt-inside-inner-col > .kb-image6565_a83b43-42 .kb-image-is-ratio-size{align-self:unset;}.kb-image6565_a83b43-42 figure{max-width:439px;}.kb-image6565_a83b43-42 .image-is-svg, .kb-image6565_a83b43-42 .image-is-svg img{width:100%;}.kb-image6565_a83b43-42 .kb-image-has-overlay:after{opacity:0.3;}<\/style>\n<div class=\"wp-block-kadence-image kb-image6565_a83b43-42\"><figure class=\"aligncenter\"><img decoding=\"async\" width=\"622\" height=\"623\" src=\"https:\/\/www.waters.com\/blog\/wp-content\/uploads\/dr_stuart_best.jpg\" alt=\"Dr. Stuart Best\" class=\"kb-img wp-image-6573\" srcset=\"https:\/\/www.waters.com\/blog\/wp-content\/uploads\/dr_stuart_best.jpg 622w, https:\/\/www.waters.com\/blog\/wp-content\/uploads\/dr_stuart_best-300x300.jpg 300w, https:\/\/www.waters.com\/blog\/wp-content\/uploads\/dr_stuart_best-150x150.jpg 150w, https:\/\/www.waters.com\/blog\/wp-content\/uploads\/dr_stuart_best-350x350.jpg 350w\" sizes=\"(max-width: 622px) 100vw, 622px\" \/><figcaption><em>Dr. Stuart Best, Deputy Director of DMPK at<\/em> <em>Sygnature Discovery.<\/em><\/figcaption><\/figure><\/div>\n<\/div>\n\n\n<style>.wp-block-kadence-spacer.kt-block-spacer-6565_70682d-8f .kt-block-spacer{height:29px;}.wp-block-kadence-spacer.kt-block-spacer-6565_70682d-8f .kt-divider{border-top-width:1px;height:1px;border-top-color:#eee;width:80%;border-top-style:solid;}<\/style>\n<div class=\"wp-block-kadence-spacer aligncenter kt-block-spacer-6565_70682d-8f\"><div class=\"kt-block-spacer kt-block-spacer-halign-center\"><hr class=\"kt-divider\"\/><\/div><\/div>\n\n\n<style>.wp-block-kadence-advancedheading.kt-adv-heading6565_d05424-bb, .wp-block-kadence-advancedheading.kt-adv-heading6565_d05424-bb[data-kb-block=\"kb-adv-heading6565_d05424-bb\"]{font-style:normal;}.wp-block-kadence-advancedheading.kt-adv-heading6565_d05424-bb mark.kt-highlight, .wp-block-kadence-advancedheading.kt-adv-heading6565_d05424-bb[data-kb-block=\"kb-adv-heading6565_d05424-bb\"] mark.kt-highlight{font-style:normal;color:#f76a0c;-webkit-box-decoration-break:clone;box-decoration-break:clone;padding-top:0px;padding-right:0px;padding-bottom:0px;padding-left:0px;}.wp-block-kadence-advancedheading.kt-adv-heading6565_d05424-bb img.kb-inline-image, .wp-block-kadence-advancedheading.kt-adv-heading6565_d05424-bb[data-kb-block=\"kb-adv-heading6565_d05424-bb\"] img.kb-inline-image{width:150px;vertical-align:baseline;}<\/style>\n<h2 class=\"kt-adv-heading6565_d05424-bb wp-block-kadence-advancedheading\" data-kb-block=\"kb-adv-heading6565_d05424-bb\">What are the 3Rs in Relation to Animal Use in Drug Discovery?<\/h2>\n\n\n\n<ol class=\"wp-block-list\">\n<li>Reduction: Reducing the number of animals needed without compromising data<\/li>\n\n\n\n<li>Refinement: Real-time, minimally invasive sampling with fewer ethical concessions<\/li>\n\n\n\n<li>Replacement: Obtaining more insight per subject while reducing replication<\/li>\n<\/ol>\n\n\n\n<p class=\"wp-block-paragraph\">Addressing the core tenets behind the 3 Rs is possible by combining advanced LC-MS\/MS bioanalysis platforms and rethinking traditional pharmacokinetic\/pharmacodynamic (PK\/PD) study designs with new techniques like microdialysis.<\/p>\n\n\n<style>.wp-block-kadence-spacer.kt-block-spacer-6565_03a0e9-e0 .kt-block-spacer{height:29px;}.wp-block-kadence-spacer.kt-block-spacer-6565_03a0e9-e0 .kt-divider{border-top-width:1px;height:1px;border-top-color:#eee;width:80%;border-top-style:solid;}<\/style>\n<div class=\"wp-block-kadence-spacer aligncenter kt-block-spacer-6565_03a0e9-e0\"><div class=\"kt-block-spacer kt-block-spacer-halign-center\"><hr class=\"kt-divider\"\/><\/div><\/div>\n\n\n<style>.wp-block-kadence-advancedheading.kt-adv-heading6565_39b564-b7, .wp-block-kadence-advancedheading.kt-adv-heading6565_39b564-b7[data-kb-block=\"kb-adv-heading6565_39b564-b7\"]{font-style:normal;}.wp-block-kadence-advancedheading.kt-adv-heading6565_39b564-b7 mark.kt-highlight, .wp-block-kadence-advancedheading.kt-adv-heading6565_39b564-b7[data-kb-block=\"kb-adv-heading6565_39b564-b7\"] mark.kt-highlight{font-style:normal;color:#f76a0c;-webkit-box-decoration-break:clone;box-decoration-break:clone;padding-top:0px;padding-right:0px;padding-bottom:0px;padding-left:0px;}.wp-block-kadence-advancedheading.kt-adv-heading6565_39b564-b7 img.kb-inline-image, .wp-block-kadence-advancedheading.kt-adv-heading6565_39b564-b7[data-kb-block=\"kb-adv-heading6565_39b564-b7\"] img.kb-inline-image{width:150px;vertical-align:baseline;}<\/style>\n<h2 class=\"kt-adv-heading6565_39b564-b7 wp-block-kadence-advancedheading\" data-kb-block=\"kb-adv-heading6565_39b564-b7\">From Compromise to Confidence: The 3Rs in Action<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Historically, CNS PK\/PD studies required larger sample volumes, leading to high animal use and associated variability. Sygnature challenged this model by integrating LC-MS\/MS assays with low-volume microdialysis serial sampling techniques, dramatically reducing the number of animals needed without compromising data integrity.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">1. Reduction: Less Animal-Based Testing, More Data<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Using ultra-sensitive LC-MS\/MS technology\u2014notably the Waters Xevo\u2122 TQ Absolute Mass Spectrometer, Sygnature reliably quantified neurotransmitters and drug compounds from as little as 10-20 \u03bcL of artificial CSF (aCSF). Their optimized PK workflow reduces animal usage from 24 animals down to just three animals per study, improving ethical compliance and improving data robustness with PK profiles generated for the same animal. \u00a0<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\"><em>\u201cThis has fundamentally reduced inter-animal variability while maximizing the data we get from each study.\u201d<\/em><br>\u2014 Dr. Stuart Best,<em> <\/em>Deputy Director of Drug Metabolism and Pharmacokinetics, Sygnature Discovery<\/p>\n<\/blockquote>\n\n\n<style>.wp-block-kadence-advancedheading.kt-adv-heading6565_2ea4c9-79, .wp-block-kadence-advancedheading.kt-adv-heading6565_2ea4c9-79[data-kb-block=\"kb-adv-heading6565_2ea4c9-79\"]{font-style:normal;}.wp-block-kadence-advancedheading.kt-adv-heading6565_2ea4c9-79 mark.kt-highlight, .wp-block-kadence-advancedheading.kt-adv-heading6565_2ea4c9-79[data-kb-block=\"kb-adv-heading6565_2ea4c9-79\"] mark.kt-highlight{font-style:normal;color:#f76a0c;-webkit-box-decoration-break:clone;box-decoration-break:clone;padding-top:0px;padding-right:0px;padding-bottom:0px;padding-left:0px;}.wp-block-kadence-advancedheading.kt-adv-heading6565_2ea4c9-79 img.kb-inline-image, .wp-block-kadence-advancedheading.kt-adv-heading6565_2ea4c9-79[data-kb-block=\"kb-adv-heading6565_2ea4c9-79\"] img.kb-inline-image{width:150px;vertical-align:baseline;}<\/style>\n<h3 class=\"kt-adv-heading6565_2ea4c9-79 wp-block-kadence-advancedheading\" data-kb-block=\"kb-adv-heading6565_2ea4c9-79\">2. Refinement: Real-Time Monitoring with Microdialysis<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Microdialysis enables real-time serial CNS sampling in conscious animals, eliminating the need for terminal single timepoint procedures. As LC-MS\/MS technologies continue to become more sensitive, this approach, even with its low sample volumes, delivers insightful data.<\/p>\n\n\n<style>.wp-block-kadence-advancedheading.kt-adv-heading6565_af26c2-30, .wp-block-kadence-advancedheading.kt-adv-heading6565_af26c2-30[data-kb-block=\"kb-adv-heading6565_af26c2-30\"]{font-style:normal;}.wp-block-kadence-advancedheading.kt-adv-heading6565_af26c2-30 mark.kt-highlight, .wp-block-kadence-advancedheading.kt-adv-heading6565_af26c2-30[data-kb-block=\"kb-adv-heading6565_af26c2-30\"] mark.kt-highlight{font-style:normal;color:#f76a0c;-webkit-box-decoration-break:clone;box-decoration-break:clone;padding-top:0px;padding-right:0px;padding-bottom:0px;padding-left:0px;}.wp-block-kadence-advancedheading.kt-adv-heading6565_af26c2-30 img.kb-inline-image, .wp-block-kadence-advancedheading.kt-adv-heading6565_af26c2-30[data-kb-block=\"kb-adv-heading6565_af26c2-30\"] img.kb-inline-image{width:150px;vertical-align:baseline;}<\/style>\n<h3 class=\"kt-adv-heading6565_af26c2-30 wp-block-kadence-advancedheading\" data-kb-block=\"kb-adv-heading6565_af26c2-30\">3. Replacement: Smarter Study Design, Less Animal Dependence<\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Full replacement of animal models remains a long-term goal, but Sygnature\u2019s approach shifts the paradigm. By extracting more insight per subject and reducing unnecessary replication, their team demonstrates that ethical, data-rich CNS research is not only possible\u2014 but scalable.<\/p>\n\n\n<style>.wp-block-kadence-spacer.kt-block-spacer-6565_b960f8-10 .kt-block-spacer{height:29px;}.wp-block-kadence-spacer.kt-block-spacer-6565_b960f8-10 .kt-divider{border-top-width:1px;height:1px;border-top-color:#eee;width:80%;border-top-style:solid;}<\/style>\n<div class=\"wp-block-kadence-spacer aligncenter kt-block-spacer-6565_b960f8-10\"><div class=\"kt-block-spacer kt-block-spacer-halign-center\"><hr class=\"kt-divider\"\/><\/div><\/div>\n\n\n<style>.wp-block-kadence-advancedheading.kt-adv-heading6565_f6d332-b8, .wp-block-kadence-advancedheading.kt-adv-heading6565_f6d332-b8[data-kb-block=\"kb-adv-heading6565_f6d332-b8\"]{font-style:normal;}.wp-block-kadence-advancedheading.kt-adv-heading6565_f6d332-b8 mark.kt-highlight, .wp-block-kadence-advancedheading.kt-adv-heading6565_f6d332-b8[data-kb-block=\"kb-adv-heading6565_f6d332-b8\"] mark.kt-highlight{font-style:normal;color:#f76a0c;-webkit-box-decoration-break:clone;box-decoration-break:clone;padding-top:0px;padding-right:0px;padding-bottom:0px;padding-left:0px;}.wp-block-kadence-advancedheading.kt-adv-heading6565_f6d332-b8 img.kb-inline-image, .wp-block-kadence-advancedheading.kt-adv-heading6565_f6d332-b8[data-kb-block=\"kb-adv-heading6565_f6d332-b8\"] img.kb-inline-image{width:150px;vertical-align:baseline;}<\/style>\n<h2 class=\"kt-adv-heading6565_f6d332-b8 wp-block-kadence-advancedheading\" data-kb-block=\"kb-adv-heading6565_f6d332-b8\">A New Era of CNS Bioanalysis: Supported by Waters<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Sygnature Discovery\u2019s approach highlights how cutting-edge technology enables both scientific and ethical progress. Leveraging Waters UPLC\u2122 and tandem quadrupole MS systems, including the Xevo TQ Absolute and ACQUITY\u2122 UPLC Systems, they\u2019ve redefined what\u2019s possible in low-volume, high-throughput CNS bioanalysis.<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\"><em>\u201cOur ability to perform high-sensitivity CNS bioanalysis from such small volumes is a game-changer\u2014for both the science and the animals.\u201d<\/em><br>\u2014 Dr. Stuart Best<a id=\"_msocom_1\"><\/a><\/p>\n<\/blockquote>\n\n\n<style>.wp-block-kadence-spacer.kt-block-spacer-6565_e0c2f3-05 .kt-block-spacer{height:29px;}.wp-block-kadence-spacer.kt-block-spacer-6565_e0c2f3-05 .kt-divider{border-top-width:1px;height:1px;border-top-color:#eee;width:80%;border-top-style:solid;}<\/style>\n<div class=\"wp-block-kadence-spacer aligncenter kt-block-spacer-6565_e0c2f3-05\"><div class=\"kt-block-spacer kt-block-spacer-halign-center\"><hr class=\"kt-divider\"\/><\/div><\/div>\n\n\n<style>.wp-block-kadence-advancedheading.kt-adv-heading6565_21f48d-f4, .wp-block-kadence-advancedheading.kt-adv-heading6565_21f48d-f4[data-kb-block=\"kb-adv-heading6565_21f48d-f4\"]{font-style:normal;}.wp-block-kadence-advancedheading.kt-adv-heading6565_21f48d-f4 mark.kt-highlight, .wp-block-kadence-advancedheading.kt-adv-heading6565_21f48d-f4[data-kb-block=\"kb-adv-heading6565_21f48d-f4\"] mark.kt-highlight{font-style:normal;color:#f76a0c;-webkit-box-decoration-break:clone;box-decoration-break:clone;padding-top:0px;padding-right:0px;padding-bottom:0px;padding-left:0px;}.wp-block-kadence-advancedheading.kt-adv-heading6565_21f48d-f4 img.kb-inline-image, .wp-block-kadence-advancedheading.kt-adv-heading6565_21f48d-f4[data-kb-block=\"kb-adv-heading6565_21f48d-f4\"] img.kb-inline-image{width:150px;vertical-align:baseline;}<\/style>\n<h2 class=\"kt-adv-heading6565_21f48d-f4 wp-block-kadence-advancedheading\" data-kb-block=\"kb-adv-heading6565_21f48d-f4\">Why CNS Bioanalysis Matters<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Sygnature Discovery\u2019s integrated approach enables:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>High-throughput, high-sensitivity CNS bioanalysis<\/li>\n\n\n\n<li>Ethical animal studies aligned with the 3Rs<\/li>\n\n\n\n<li>Comprehensive PK\/PD modelling from minimal sample volumes<\/li>\n<\/ul>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\"><em>\u201cLC-MS\/MS has transformed our ability to maximize bioanalytical data from the smallest possible samples. It\u2019s invaluable for CNS discovery.\u201d<\/em><br>\u2014 Dr. Stuart Best<\/p>\n<\/blockquote>\n\n\n<style>.wp-block-kadence-spacer.kt-block-spacer-6565_1055ee-4f .kt-block-spacer{height:29px;}.wp-block-kadence-spacer.kt-block-spacer-6565_1055ee-4f .kt-divider{border-top-width:1px;height:1px;border-top-color:#eee;width:80%;border-top-style:solid;}<\/style>\n<div class=\"wp-block-kadence-spacer aligncenter kt-block-spacer-6565_1055ee-4f\"><div class=\"kt-block-spacer kt-block-spacer-halign-center\"><hr class=\"kt-divider\"\/><\/div><\/div>\n\n\n<style>.wp-block-kadence-advancedheading.kt-adv-heading6565_9b8d49-bb, .wp-block-kadence-advancedheading.kt-adv-heading6565_9b8d49-bb[data-kb-block=\"kb-adv-heading6565_9b8d49-bb\"]{font-style:normal;}.wp-block-kadence-advancedheading.kt-adv-heading6565_9b8d49-bb mark.kt-highlight, .wp-block-kadence-advancedheading.kt-adv-heading6565_9b8d49-bb[data-kb-block=\"kb-adv-heading6565_9b8d49-bb\"] mark.kt-highlight{font-style:normal;color:#f76a0c;-webkit-box-decoration-break:clone;box-decoration-break:clone;padding-top:0px;padding-right:0px;padding-bottom:0px;padding-left:0px;}.wp-block-kadence-advancedheading.kt-adv-heading6565_9b8d49-bb img.kb-inline-image, .wp-block-kadence-advancedheading.kt-adv-heading6565_9b8d49-bb[data-kb-block=\"kb-adv-heading6565_9b8d49-bb\"] img.kb-inline-image{width:150px;vertical-align:baseline;}<\/style>\n<h2 class=\"kt-adv-heading6565_9b8d49-bb wp-block-kadence-advancedheading\" data-kb-block=\"kb-adv-heading6565_9b8d49-bb\">Ready to Learn More?<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">&nbsp;Dr. Stuart Best\u2019s presentation is part of <em>Navigating an Evolving Landscape in DMPK: Bioanalysis and Beyond- <\/em>a webinar series from Waters that explores how the pharmaceutical industry is adapting to emerging modalities and ethical research practices through advanced bioanalytical technologies.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In this 30-minute on-demand session, \u201c<em>More from Less: LC-MS\/MS \u2013 An Enabling Technology to Maximize Bioanalytical Data Collection from Small Sample Volumes\u201d<\/em>, Dr. Best shares how Sygnature Discovery is generating high-quality CNS data from low-volume samples while aligning with the 3Rs principles of ethical research.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><a href=\"https:\/\/event.on24.com\/eventRegistration\/EventLobbyServlet?target=reg20.jsp&amp;eventid=4733147&amp;sessionid=1&amp;key=04DC16A251252FD1A99E4730FFBA7015&amp;groupId=5759526&amp;sourcepage=register&amp;partnerref=MoreFromLessBlog\"><strong>Watch now<\/strong><\/a> <\/p>\n","protected":false},"excerpt":{"rendered":"<p>How Sygnature Discovery Supports the 3Rs with LC-MS\/MS Scientific Precision and Ethical Innovation In the world of drug discovery, researchers face a critical challenge: how do you generate high-quality, reproducible bioanalytical data while minimizing the ethical and logistical burden of using animals in testing?&nbsp; 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