{"id":47650,"date":"2026-07-24T08:49:02","date_gmt":"2026-07-24T06:49:02","guid":{"rendered":"https:\/\/kymos.com\/news\/bioanalyse-des-acides-nucleiques-elargir-les-capacites-analytiques-avec-la-lc-ms-ms\/"},"modified":"2026-07-24T08:56:17","modified_gmt":"2026-07-24T06:56:17","slug":"bioanalyse-des-acides-nucleiques-elargir-les-capacites-analytiques-avec-la-lc-ms-ms","status":"publish","type":"post","link":"https:\/\/kymos.com\/fr\/news\/bioanalyse-des-acides-nucleiques-elargir-les-capacites-analytiques-avec-la-lc-ms-ms\/","title":{"rendered":"Bioanalyse des acides nucl\u00e9iques : \u00e9largir les capacit\u00e9s analytiques avec la LC-MS\/MS"},"content":{"rendered":"<div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-1 fusion-flex-container has-pattern-background has-mask-background nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-padding-top:0px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap\" style=\"max-width:calc( 1170px + 20px );margin-left: calc(-20px \/ 2 );margin-right: calc(-20px \/ 2 );\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-0 fusion_builder_column_1_1 1_1 fusion-flex-column\" style=\"--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:10px;--awb-margin-bottom-large:20px;--awb-spacing-left-large:10px;--awb-width-medium:100%;--awb-order-medium:0;--awb-spacing-right-medium:10px;--awb-spacing-left-medium:10px;--awb-width-small:100%;--awb-order-small:0;--awb-spacing-right-small:10px;--awb-spacing-left-small:10px;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column\"><div class=\"fusion-text fusion-text-1\"><p><span style=\"background-color: rgba(0, 0, 0, 0); font-size: 14pt;\">Les th\u00e9rapies \u00e0 base d&rsquo;acides nucl\u00e9iques sont devenues l&rsquo;une des classes de m\u00e9dicaments innovants connaissant la croissance la plus rapide, offrant de nouvelles opportunit\u00e9s de traitement pour des maladies traditionnellement difficiles \u00e0 traiter avec des petites mol\u00e9cules ou des produits biologiques conventionnels. Les oligonucl\u00e9otides antisens (ASO), les petits ARN interf\u00e9rents (siRNA), les aptam\u00e8res, les th\u00e9rapies \u00e0 ARN messager (mRNA) et d&rsquo;autres modalit\u00e9s \u00e0 base d&rsquo;acides nucl\u00e9iques progressent rapidement dans le d\u00e9veloppement de m\u00e9dicaments, ce qui n\u00e9cessite des m\u00e9thodes bioanalytiques robustes capables de caract\u00e9riser avec pr\u00e9cision ces mol\u00e9cules complexes (1,2). <\/span><\/p>\n<p><span style=\"font-size: 14pt;\">Compar\u00e9s aux petites mol\u00e9cules traditionnelles, les oligonucl\u00e9otides th\u00e9rapeutiques pr\u00e9sentent des d\u00e9fis analytiques uniques. Leur taille mol\u00e9culaire relativement importante, leur forte polarit\u00e9 et leur susceptibilit\u00e9 \u00e0 la d\u00e9gradation par les nucl\u00e9ases compliquent l&rsquo;extraction et la quantification \u00e0 partir de matrices biologiques. De plus, ils g\u00e9n\u00e8rent souvent des m\u00e9tabolites tronqu\u00e9s qui peuvent diff\u00e9rer du compos\u00e9 parent par un seul nucl\u00e9otide tout en pr\u00e9sentant des propri\u00e9t\u00e9s pharmacologiques ou toxicologiques distinctes. Par cons\u00e9quent, des m\u00e9thodes bioanalytiques sensibles et s\u00e9lectives sont essentielles pour soutenir les \u00e9tudes pharmacocin\u00e9tiques, toxicocin\u00e9tiques, de biodistribution et de biomarqueurs (1\u20133).   <\/span><\/p>\n<p><span style=\"font-size: 14pt;\">Chez Kymos, nous soutenons la bioanalyse des th\u00e9rapies \u00e0 base d&rsquo;acides nucl\u00e9iques en utilisant des m\u00e9thodologies de biologie mol\u00e9culaire et de spectrom\u00e9trie de masse, en d\u00e9veloppant des m\u00e9thodes analytiques adapt\u00e9es \u00e0 l&rsquo;objectif pour les \u00e9tudes pr\u00e9cliniques et cliniques.<\/span><\/p>\n<h2><strong>Approches bioanalytiques pour les th\u00e9rapies \u00e0 base d&rsquo;acides nucl\u00e9iques<\/strong><\/h2>\n<p><span style=\"font-size: 14pt;\">La strat\u00e9gie analytique d\u00e9pend \u00e0 la fois de la modalit\u00e9 th\u00e9rapeutique et des objectifs de chaque \u00e9tude. \u00c9tant donn\u00e9 qu&rsquo;aucune technologie unique ne peut r\u00e9pondre \u00e0 toutes les questions analytiques, des techniques analytiques compl\u00e9mentaires sont souvent combin\u00e9es pour r\u00e9pondre \u00e0 diff\u00e9rents objectifs bioanalytiques. Chez Kymos, ces approches comprennent :  <\/span><\/p>\n<ul>\n<li><span style=\"font-size: 14pt;\">Quantification de biomarqueurs \u00e0 l&rsquo;aide de la PCR quantitative en temps r\u00e9el (qPCR) hautement sensible, avec une d\u00e9tection jusqu&rsquo;\u00e0 1 pg\/mL.<\/span><\/li>\n<li><span style=\"font-size: 14pt;\">Quantification d&rsquo;oligonucl\u00e9otides th\u00e9rapeutiques \u00e0 l&rsquo;aide d&rsquo;ELISA par hybridation, de qPCR et de LC-MS\/MS.<\/span><\/li>\n<li><span style=\"font-size: 14pt;\">Quantification d&rsquo;ADN, d&rsquo;ARNm, de siRNA, d&rsquo;aptam\u00e8res et d&rsquo;antagomiR.<\/span><\/li>\n<li><span style=\"font-size: 14pt;\">Analyse de l&rsquo;expression g\u00e9nique \u00e0 l&rsquo;aide de la m\u00e9thode \u0394\u0394Ct.<\/span><\/li>\n<li><span style=\"font-size: 14pt;\">D\u00e9tection d&rsquo;ADN ou d&rsquo;ARN viral et bact\u00e9rien.<\/span><\/li>\n<li><span style=\"font-size: 14pt;\">\u00c9tudes de biodistribution pour les th\u00e9rapies et vaccins \u00e0 base d&rsquo;ADN et d&rsquo;ARN.<\/span><\/li>\n<li><span style=\"font-size: 14pt;\">Analyse de l&rsquo;ADN humain r\u00e9siduel pour \u00e9valuer l&rsquo;efficacit\u00e9 de la d\u00e9cellularisation des allogreffes.<\/span><\/li>\n<\/ul>\n<p><span style=\"font-size: 14pt;\">Bien que la qPCR reste la m\u00e9thode de choix pour de nombreuses applications de biomarqueurs et d&rsquo;expression g\u00e9nique, la complexit\u00e9 croissante des oligonucl\u00e9otides th\u00e9rapeutiques a conduit \u00e0 l&rsquo;adoption de technologies analytiques compl\u00e9mentaires offrant une plus grande sp\u00e9cificit\u00e9 mol\u00e9culaire et une meilleure caract\u00e9risation des m\u00e9tabolites.<\/span><\/p>\n<h2><strong>LC-MS\/MS : \u00e9largir la bo\u00eete \u00e0 outils analytique<\/strong><\/h2>\n<p><span style=\"font-size: 14pt;\">Les progr\u00e8s r\u00e9cents de la chromatographie liquide coupl\u00e9e \u00e0 la spectrom\u00e9trie de masse en tandem (LC-MS\/MS) ont consid\u00e9rablement \u00e9largi la bo\u00eete \u00e0 outils analytique disponible pour les oligonucl\u00e9otides th\u00e9rapeutiques (2\u20134). Contrairement aux dosages ELISA par hybridation, la LC-MS\/MS identifie directement les analytes en fonction de leur masse mol\u00e9culaire et de leurs profils de fragmentation caract\u00e9ristiques, permettant une quantification pr\u00e9cise du compos\u00e9 parent ainsi que la discrimination de m\u00e9tabolites \u00e9troitement apparent\u00e9s. Contrairement aux m\u00e9thodes bas\u00e9es sur l&rsquo;hybridation, la LC-MS\/MS fournit une d\u00e9tection mol\u00e9culaire directe, permettant non seulement une quantification pr\u00e9cise mais aussi une confirmation structurelle de l&rsquo;analyte. Ce niveau suppl\u00e9mentaire de sp\u00e9cificit\u00e9 est particuli\u00e8rement pr\u00e9cieux lors de l&rsquo;analyse d&rsquo;oligonucl\u00e9otides chimiquement modifi\u00e9s ou de la distinction de m\u00e9tabolites \u00e9troitement apparent\u00e9s qui peuvent ne pas \u00eatre diff\u00e9renci\u00e9s en utilisant uniquement des dosages bas\u00e9s sur des sondes.   <\/span><\/p>\n<p><span style=\"font-size: 14pt;\">Cette capacit\u00e9 est particuli\u00e8rement pr\u00e9cieuse car les oligonucl\u00e9otides th\u00e9rapeutiques subissent fr\u00e9quemment une d\u00e9gradation m\u00e9di\u00e9e par les exonucl\u00e9ases, produisant des m\u00e9tabolites raccourcis tels que les esp\u00e8ces N\u22121 qui peuvent contribuer \u00e0 l&rsquo;efficacit\u00e9 ou \u00e0 la s\u00e9curit\u00e9. La LC-MS\/MS est \u00e9galement bien adapt\u00e9e aux oligonucl\u00e9otides chimiquement modifi\u00e9s, y compris les oligonucl\u00e9otides phosphorothioates et les mol\u00e9cules conjugu\u00e9es \u00e0 des ligands, offrant une sp\u00e9cificit\u00e9 analytique \u00e9lev\u00e9e et une confiance dans l&rsquo;identification de l&rsquo;analyte (1\u20134). <\/span><\/p>\n<p><span style=\"font-size: 14pt;\">Les m\u00e9thodes LC-MS\/MS chez Kymos soutiennent l&rsquo;analyse d&rsquo;oligonucl\u00e9otides th\u00e9rapeutiques dans le plasma et les homog\u00e9nats de tissus. L&rsquo;hybridation sur billes magn\u00e9tiques sp\u00e9cifiques de s\u00e9quence permet une purification s\u00e9lective de l&rsquo;\u00e9chantillon avant l&rsquo;analyse quantitative par LC-MS\/MS sur des gammes de concentration g\u00e9n\u00e9ralement comprises entre 1 et 1 000 ng\/mL. <\/span><\/p>\n<h2><strong>Hybridation sur billes magn\u00e9tiques : la cl\u00e9 d&rsquo;une pr\u00e9paration s\u00e9lective des \u00e9chantillons<\/strong><\/h2>\n<p><span style=\"font-size: 14pt;\">Une pr\u00e9paration efficace des \u00e9chantillons est essentielle pour une bioanalyse LC-MS\/MS r\u00e9ussie. Les matrices biologiques contiennent des prot\u00e9ines, des phospholipides et des acides nucl\u00e9iques endog\u00e8nes qui peuvent interf\u00e9rer avec la d\u00e9tection par spectrom\u00e9trie de masse. Pour surmonter ces d\u00e9fis, Kymos utilise l&rsquo;hybridation sur billes magn\u00e9tiques sp\u00e9cifiques de s\u00e9quence avant l&rsquo;analyse LC-MS\/MS (1,2).  <\/span><\/p>\n<p><span style=\"font-size: 14pt;\">Les particules magn\u00e9tiques sont fonctionnalis\u00e9es avec des sondes oligonucl\u00e9otidiques de capture compl\u00e9mentaires \u00e0 la s\u00e9quence th\u00e9rapeutique d&rsquo;int\u00e9r\u00eat. Les sondes de capture sont immobilis\u00e9es sur la surface des billes magn\u00e9tiques, g\u00e9n\u00e9ralement par des interactions biotine-streptavidine, assurant une liaison stable et hautement s\u00e9lective tout au long du processus d&rsquo;extraction. Apr\u00e8s l&rsquo;hybridation, un s\u00e9parateur magn\u00e9tique isole les complexes bille-cible tandis que la matrice biologique restante est \u00e9limin\u00e9e. Les prot\u00e9ines, les phospholipides et autres composants matriciels endog\u00e8nes sont efficacement \u00e9limin\u00e9s lors des \u00e9tapes de lavage ult\u00e9rieures, et une \u00e9lution contr\u00f4l\u00e9e lib\u00e8re l&rsquo;oligonucl\u00e9otide purifi\u00e9 pour l&rsquo;analyse LC-MS\/MS.   <\/span><\/p>\n<p><span style=\"font-size: 14pt;\">Ce flux de travail est rapide, hautement s\u00e9lectif et compatible avec les plateformes de manipulation de liquides automatis\u00e9es, ce qui le rend adapt\u00e9 aux \u00e9tudes \u00e0 haut d\u00e9bit. Compar\u00e9e aux m\u00e9thodes d&rsquo;extraction conventionnelles, l&rsquo;hybridation sur billes magn\u00e9tiques offre plusieurs avantages : <\/span><\/p>\n<ul>\n<li><span style=\"font-size: 14pt;\">Sp\u00e9cificit\u00e9 de s\u00e9quence \u00e9lev\u00e9e.<\/span><\/li>\n<li><span style=\"font-size: 14pt;\">Purification efficace \u00e0 partir de matrices biologiques complexes.<\/span><\/li>\n<li><span style=\"font-size: 14pt;\">Effets matriciels et suppression d&rsquo;ions r\u00e9duits.<\/span><\/li>\n<li><span style=\"font-size: 14pt;\">Excellente reproductibilit\u00e9 et faible report d&rsquo;\u00e9chantillon.<\/span><\/li>\n<li><span style=\"font-size: 14pt;\">Compatibilit\u00e9 avec les flux de travail automatis\u00e9s \u00e0 haut d\u00e9bit.<\/span><\/li>\n<li><span style=\"font-size: 14pt;\">Discrimination pr\u00e9cise de m\u00e9tabolites \u00e9troitement apparent\u00e9s, y compris les produits de d\u00e9gradation N\u22121 (1,2,4).<\/span><\/li>\n<\/ul>\n<p><span style=\"font-size: 14pt;\">En combinant un enrichissement s\u00e9lectif avec une d\u00e9tection LC-MS\/MS hautement sp\u00e9cifique, ce flux de travail int\u00e9gr\u00e9 permet une quantification robuste des oligonucl\u00e9otides th\u00e9rapeutiques dans des matrices biologiques complexes, soutenant les \u00e9tudes pharmacocin\u00e9tiques, de biodistribution et de m\u00e9tabolisme.<\/span><\/p>\n<\/div><div class=\"fusion-image-element \" style=\"--awb-caption-title-font-family:var(--h2_typography-font-family);--awb-caption-title-font-weight:var(--h2_typography-font-weight);--awb-caption-title-font-style:var(--h2_typography-font-style);--awb-caption-title-size:var(--h2_typography-font-size);--awb-caption-title-transform:var(--h2_typography-text-transform);--awb-caption-title-line-height:var(--h2_typography-line-height);--awb-caption-title-letter-spacing:var(--h2_typography-letter-spacing);\"><span class=\" fusion-imageframe imageframe-none imageframe-1 hover-type-none\"><img decoding=\"async\" width=\"1536\" height=\"1024\" title=\"LC-MS_MS Bioanalysis Workflow\" src=\"https:\/\/kymos.com\/wp-content\/uploads\/2026\/07\/LC-MS_MS-Bioanalysis-Workflow.png\" data-orig-src=\"https:\/\/kymos.com\/wp-content\/uploads\/2026\/07\/LC-MS_MS-Bioanalysis-Workflow.png\" alt class=\"lazyload img-responsive wp-image-47614\" srcset=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%271536%27%20height%3D%271024%27%20viewBox%3D%270%200%201536%201024%27%3E%3Crect%20width%3D%271536%27%20height%3D%271024%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E\" data-srcset=\"https:\/\/kymos.com\/wp-content\/uploads\/2026\/07\/LC-MS_MS-Bioanalysis-Workflow-200x133.png 200w, https:\/\/kymos.com\/wp-content\/uploads\/2026\/07\/LC-MS_MS-Bioanalysis-Workflow-400x267.png 400w, https:\/\/kymos.com\/wp-content\/uploads\/2026\/07\/LC-MS_MS-Bioanalysis-Workflow-600x400.png 600w, https:\/\/kymos.com\/wp-content\/uploads\/2026\/07\/LC-MS_MS-Bioanalysis-Workflow-800x533.png 800w, https:\/\/kymos.com\/wp-content\/uploads\/2026\/07\/LC-MS_MS-Bioanalysis-Workflow-1200x800.png 1200w, https:\/\/kymos.com\/wp-content\/uploads\/2026\/07\/LC-MS_MS-Bioanalysis-Workflow.png 1536w\" data-sizes=\"auto\" data-orig-sizes=\"(max-width: 850px) 100vw, 1200px\" \/><\/span><\/div><div class=\"fusion-text fusion-text-2\"><p>&nbsp;<\/p>\n<h2><strong>Soutenir la prochaine g\u00e9n\u00e9ration de th\u00e9rapies \u00e0 base d&rsquo;acides nucl\u00e9iques<\/strong><\/h2>\n<p><span style=\"font-size: 14pt;\">Les m\u00e9dicaments \u00e0 base d&rsquo;acides nucl\u00e9iques continuent d&rsquo;\u00e9voluer, et les m\u00e9thodologies bioanalytiques doivent \u00e9galement progresser pour r\u00e9pondre \u00e0 leur complexit\u00e9 croissante. Plut\u00f4t que de remplacer les techniques \u00e9tablies telles que la qPCR ou l&rsquo;ELISA par hybridation, la LC-MS\/MS compl\u00e8te ces approches en fournissant une sp\u00e9cificit\u00e9 mol\u00e9culaire am\u00e9lior\u00e9e et une discrimination des m\u00e9tabolites (2\u20134). <\/span><\/p>\n<p><span style=\"font-size: 14pt;\">En combinant une expertise en biologie mol\u00e9culaire avec des capacit\u00e9s avanc\u00e9es de spectrom\u00e9trie de masse, Kymos fournit des solutions bioanalytiques adapt\u00e9es \u00e0 chaque modalit\u00e9 th\u00e9rapeutique et \u00e9tude. L&rsquo;int\u00e9gration de techniques analytiques compl\u00e9mentaires permet une caract\u00e9risation plus compl\u00e8te des oligonucl\u00e9otides th\u00e9rapeutiques, soutenant les \u00e9tudes pharmacocin\u00e9tiques, de biodistribution et de m\u00e9tabolisme tout en fournissant les donn\u00e9es fiables n\u00e9cessaires pour acc\u00e9l\u00e9rer le d\u00e9veloppement de la prochaine g\u00e9n\u00e9ration de m\u00e9dicaments \u00e0 base d&rsquo;acides nucl\u00e9iques. <\/span><\/p>\n<h3><strong>R\u00e9f\u00e9rences<\/strong><\/h3>\n<ol>\n<li>Rooney M, Ji QC, Leung K, et al.  <em>Hybridization Liquid Chromatography-Tandem Mass Spectrometry: An Alternative Bioanalytical Method for Antisense Oligonucleotide Quantitation in Plasma and Tissue Samples.<\/em>  Analytical Chemistry. 2020;92(15):10239-10247. <\/li>\n<li>Yuan L. <em>Hybridization Liquid Chromatography-Mass Spectrometry for Quantitative Bioanalysis of Oligonucleotides: The Upcoming Paradigm Shift.<\/em> Journal of Chromatography A. 2026;1766:466575.<\/li>\n<li>Yuan L. Bioanalysis of Oligonucleotides. In: Ahuja S, Dong MW, editors.   <em>Specification of Drug Substances and Products: Development and Validation of Analytical Methods.<\/em>  Elsevier; 2025. p. 209-243. <\/li>\n<li>Gilar M, Biba M, DeLano M, et al.  <em>Bioanalysis of Oligonucleotide by LC-MS: Effects of Ion Pairing Reagents and Recent Advances in Ion-Pairing-Free Analytical Strategies.<\/em>  Molecules. 2022;27(23):8875. <\/li>\n<li>European Medicines Agency.  <em>Guideline on Bioanalytical Method Validation.<\/em>  EMA; 2011.<\/li>\n<li>Resolve Mass Spectrometry. <em>LC-MS Bioanalysis for Oligonucleotides.<\/em> Available at: <a href=\"https:\/\/resolvemass.ca\/lc-ms-bioanalysis-for-oligonucleotides\/\" data-wpel-link=\"external\">https:\/\/resolvemass.ca\/lc-ms-bioanalysis-for-oligonucleotides\/<\/a> (accessed July 2026).<\/li>\n<\/ol>\n<\/div><\/div><\/div><\/div><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":8,"featured_media":47604,"comment_status":"closed","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[257],"tags":[],"class_list":["post-47650","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-bioanalyse"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.1 - 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