Volumetric absorptive microsampling coupled with hybridization LC-MS/MS for quantitation of antisense oligonucleotides
Background: Volumetric absorptive microsampling has emerged as a less invasive alternative to venous sampling for small-molecule pharmacokinetic studies, but its application to novel therapeutics such as antisense oligonucleotides (ASOs) is not well-established. Results: A workflow was developed using Mitra microsampling coupled with hybridization LC-MS/MS for accurate determination of fomivirsen, a 21-mer ASO, in human blood. Quantitative recovery was achieved regardless of blood hematocrit level or microsample age by implementing impact-assisted extraction. A thorough method evaluation confirmed sensitivity, linearity, precision/accuracy, matrix effect, metabolite interference and four months of microsample stability. Conclusion: The combined impact-assisted extraction and hybridization LC-MS/MS workflow demonstrated the successful quantitation of fomivirsen, establishing the validity and applicability of the approach for ASO drug candidates.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Bioanalysis - 15(2023), 18 vom: 19. Sept., Seite 1115-1128 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Chen, Ming-Luan [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antisense oligonucleotides |
|---|
| Anmerkungen: |
Date Completed 18.09.2023 Date Revised 18.09.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.4155/bio-2023-0092 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM361791194 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM361791194 | ||
| 003 | DE-627 | ||
| 005 | 20231226085901.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.4155/bio-2023-0092 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1205.xml |
| 035 | |a (DE-627)NLM361791194 | ||
| 035 | |a (NLM)37681562 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Chen, Ming-Luan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Volumetric absorptive microsampling coupled with hybridization LC-MS/MS for quantitation of antisense oligonucleotides |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 18.09.2023 | ||
| 500 | |a Date Revised 18.09.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Background: Volumetric absorptive microsampling has emerged as a less invasive alternative to venous sampling for small-molecule pharmacokinetic studies, but its application to novel therapeutics such as antisense oligonucleotides (ASOs) is not well-established. Results: A workflow was developed using Mitra microsampling coupled with hybridization LC-MS/MS for accurate determination of fomivirsen, a 21-mer ASO, in human blood. Quantitative recovery was achieved regardless of blood hematocrit level or microsample age by implementing impact-assisted extraction. A thorough method evaluation confirmed sensitivity, linearity, precision/accuracy, matrix effect, metabolite interference and four months of microsample stability. Conclusion: The combined impact-assisted extraction and hybridization LC-MS/MS workflow demonstrated the successful quantitation of fomivirsen, establishing the validity and applicability of the approach for ASO drug candidates | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Mitra® volumetric absorptive microsampling | |
| 650 | 4 | |a antisense oligonucleotides | |
| 650 | 4 | |a fomivirsen | |
| 650 | 4 | |a hybridization LC–MS/MS | |
| 650 | 4 | |a impact-assisted extraction | |
| 650 | 7 | |a fomivirsen |2 NLM | |
| 650 | 7 | |a QX5LK7YCHV |2 NLM | |
| 650 | 7 | |a Oligonucleotides, Antisense |2 NLM | |
| 700 | 1 | |a Mekhssian, Kevork |e verfasserin |4 aut | |
| 700 | 1 | |a Dutt, Muskaan |e verfasserin |4 aut | |
| 700 | 1 | |a Plomley, Jeff |e verfasserin |4 aut | |
| 700 | 1 | |a Keyhani, Anahita |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Bioanalysis |d 2009 |g 15(2023), 18 vom: 19. Sept., Seite 1115-1128 |w (DE-627)NLM196969840 |x 1757-6199 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2023 |g number:18 |g day:19 |g month:09 |g pages:1115-1128 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.4155/bio-2023-0092 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2023 |e 18 |b 19 |c 09 |h 1115-1128 | ||