Application of Parallel Reaction Monitoring to the Development and Validation of a Quantitative Assay for ST-246 in Human Plasma
In this work, we developed and validated a robust and sensitive method of liquid chromatography with high-resolution mass spectrometry in parallel reaction monitoring (PRM) mode for ST-246 (tecovirimat) quantification in human blood plasma. The method was compared with the multiple reaction monitori...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-07-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/23/14/8021 |
_version_ | 1797446416972382208 |
---|---|
author | Alexander A. Chernonosov Galina A. Oleinik Vladimir V. Koval |
author_facet | Alexander A. Chernonosov Galina A. Oleinik Vladimir V. Koval |
author_sort | Alexander A. Chernonosov |
collection | DOAJ |
description | In this work, we developed and validated a robust and sensitive method of liquid chromatography with high-resolution mass spectrometry in parallel reaction monitoring (PRM) mode for ST-246 (tecovirimat) quantification in human blood plasma. The method was compared with the multiple reaction monitoring (MRM) technique and showed better selectivity and similar sensitivity in a wider concentration range (10–5000 ng/mL). Within this range, intra- and interday variability of precision and accuracy were within acceptable ranges in accordance with the European Medicines Agency guidelines, and recovery was 87.9–100.6%. Samples were stable at 4 °C within 48 h and at −20 °C up to 3 months. The recovery and matrix effects in the proposed HRMS method were about 5% higher than those reported for the MRM method, but the PRM method showed better accuracy with comparable precision. It was found that the ST-246 concentration shown by the PRM method is approximately 24% higher than the output of the MRM one. Nonetheless, the high selectivity with similar sensitivity, as compared with traditional MRM methods, makes the proposed approach attractive for research and clinical use. |
first_indexed | 2024-03-09T13:40:13Z |
format | Article |
id | doaj.art-4d68ebd3f34d474988bbe81c0019d869 |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-09T13:40:13Z |
publishDate | 2022-07-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
spelling | doaj.art-4d68ebd3f34d474988bbe81c0019d8692023-11-30T21:07:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314802110.3390/ijms23148021Application of Parallel Reaction Monitoring to the Development and Validation of a Quantitative Assay for ST-246 in Human PlasmaAlexander A. Chernonosov0Galina A. Oleinik1Vladimir V. Koval2Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev Ave. 8, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev Ave. 8, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev Ave. 8, 630090 Novosibirsk, RussiaIn this work, we developed and validated a robust and sensitive method of liquid chromatography with high-resolution mass spectrometry in parallel reaction monitoring (PRM) mode for ST-246 (tecovirimat) quantification in human blood plasma. The method was compared with the multiple reaction monitoring (MRM) technique and showed better selectivity and similar sensitivity in a wider concentration range (10–5000 ng/mL). Within this range, intra- and interday variability of precision and accuracy were within acceptable ranges in accordance with the European Medicines Agency guidelines, and recovery was 87.9–100.6%. Samples were stable at 4 °C within 48 h and at −20 °C up to 3 months. The recovery and matrix effects in the proposed HRMS method were about 5% higher than those reported for the MRM method, but the PRM method showed better accuracy with comparable precision. It was found that the ST-246 concentration shown by the PRM method is approximately 24% higher than the output of the MRM one. Nonetheless, the high selectivity with similar sensitivity, as compared with traditional MRM methods, makes the proposed approach attractive for research and clinical use.https://www.mdpi.com/1422-0067/23/14/8021blood plasmatecovirimathigh-resolution mass spectrometryLC-HRMSPRM |
spellingShingle | Alexander A. Chernonosov Galina A. Oleinik Vladimir V. Koval Application of Parallel Reaction Monitoring to the Development and Validation of a Quantitative Assay for ST-246 in Human Plasma International Journal of Molecular Sciences blood plasma tecovirimat high-resolution mass spectrometry LC-HRMS PRM |
title | Application of Parallel Reaction Monitoring to the Development and Validation of a Quantitative Assay for ST-246 in Human Plasma |
title_full | Application of Parallel Reaction Monitoring to the Development and Validation of a Quantitative Assay for ST-246 in Human Plasma |
title_fullStr | Application of Parallel Reaction Monitoring to the Development and Validation of a Quantitative Assay for ST-246 in Human Plasma |
title_full_unstemmed | Application of Parallel Reaction Monitoring to the Development and Validation of a Quantitative Assay for ST-246 in Human Plasma |
title_short | Application of Parallel Reaction Monitoring to the Development and Validation of a Quantitative Assay for ST-246 in Human Plasma |
title_sort | application of parallel reaction monitoring to the development and validation of a quantitative assay for st 246 in human plasma |
topic | blood plasma tecovirimat high-resolution mass spectrometry LC-HRMS PRM |
url | https://www.mdpi.com/1422-0067/23/14/8021 |
work_keys_str_mv | AT alexanderachernonosov applicationofparallelreactionmonitoringtothedevelopmentandvalidationofaquantitativeassayforst246inhumanplasma AT galinaaoleinik applicationofparallelreactionmonitoringtothedevelopmentandvalidationofaquantitativeassayforst246inhumanplasma AT vladimirvkoval applicationofparallelreactionmonitoringtothedevelopmentandvalidationofaquantitativeassayforst246inhumanplasma |