Development and validation of an LC–MS/MS method for quantification of NC-8 in rat plasma and its application to pharmacokinetic studies
ent-16-Oxobeyeran-19-N-methylureido (NC-8) is a recently synthesized derivative of isosteviol that showed anti-hepatitis B virus (HBV) activity by disturbing replication and gene expression of the HBV and by inhibiting the host toll-like receptor 2/nuclear factor-κB signaling pathway. To study its p...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2018-01-01
|
Series: | Journal of Food and Drug Analysis |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1021949817301825 |
id |
doaj-f35e2149a5774d62961811c1cdd1a749 |
---|---|
record_format |
Article |
spelling |
doaj-f35e2149a5774d62961811c1cdd1a7492020-11-24T21:13:34ZengElsevierJournal of Food and Drug Analysis1021-94982018-01-0126140140810.1016/j.jfda.2017.09.003Development and validation of an LC–MS/MS method for quantification of NC-8 in rat plasma and its application to pharmacokinetic studiesBaxter Hepburn Kachingwe0Yow-Shieng Uang1Tsurng-Juhn Huang2Li-Hsuan Wang3Shwu-Jiuan Lin4School of Pharmacy, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Pharmacognosy, Taipei Medical University, Taipei 11031, TaiwanSchool of Medicine, China Medical University, Taichung 404, TaiwanSchool of Pharmacy, Taipei Medical University, Taipei 11031, TaiwanSchool of Pharmacy, Taipei Medical University, Taipei 11031, Taiwanent-16-Oxobeyeran-19-N-methylureido (NC-8) is a recently synthesized derivative of isosteviol that showed anti-hepatitis B virus (HBV) activity by disturbing replication and gene expression of the HBV and by inhibiting the host toll-like receptor 2/nuclear factor-κB signaling pathway. To study its pharmacokinetics as a part of the drug development process, a highly sensitive, rapid, and reliable liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed and validated for determining NC-8 in rat plasma. After protein precipitation extraction, the chromatographic separation of the analyte and internal standard (IS; diclofenac sodium) was performed on a reverse-phase Luna C18 column coupled with a Quattro Ultima triple quadruple mass spectrometer in the multiple-reaction monitoring mode using the transitions, m/z 347.31 → 75.09 for NC-8 and m/z 295.89 → 214.06 for the IS. The lower limit of quantitation was 0.5 ng/mL. The linear scope of the standard curve was between 0.5 and 500 ng/mL. Both the precision (coefficient of variation; %) and accuracy (relative error; %) were within acceptable criteria of <15%. Recoveries ranged from 104% to 113.4%, and the matrix effects (absolute) were non-significant (CV ≤ 6%). The validated method was successfully applied to investigate the pharmacokinetics of NC-8 in male Sprague–Dawley rats. The present methodology provides an analytical means to better understand the preliminary pharmacokinetics of NC-8 for investigations on further drug development.http://www.sciencedirect.com/science/article/pii/S1021949817301825Isosteviol derivativeLC–MS/MSNC-8Pharmacokinetics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Baxter Hepburn Kachingwe Yow-Shieng Uang Tsurng-Juhn Huang Li-Hsuan Wang Shwu-Jiuan Lin |
spellingShingle |
Baxter Hepburn Kachingwe Yow-Shieng Uang Tsurng-Juhn Huang Li-Hsuan Wang Shwu-Jiuan Lin Development and validation of an LC–MS/MS method for quantification of NC-8 in rat plasma and its application to pharmacokinetic studies Journal of Food and Drug Analysis Isosteviol derivative LC–MS/MS NC-8 Pharmacokinetics |
author_facet |
Baxter Hepburn Kachingwe Yow-Shieng Uang Tsurng-Juhn Huang Li-Hsuan Wang Shwu-Jiuan Lin |
author_sort |
Baxter Hepburn Kachingwe |
title |
Development and validation of an LC–MS/MS method for quantification of NC-8 in rat plasma and its application to pharmacokinetic studies |
title_short |
Development and validation of an LC–MS/MS method for quantification of NC-8 in rat plasma and its application to pharmacokinetic studies |
title_full |
Development and validation of an LC–MS/MS method for quantification of NC-8 in rat plasma and its application to pharmacokinetic studies |
title_fullStr |
Development and validation of an LC–MS/MS method for quantification of NC-8 in rat plasma and its application to pharmacokinetic studies |
title_full_unstemmed |
Development and validation of an LC–MS/MS method for quantification of NC-8 in rat plasma and its application to pharmacokinetic studies |
title_sort |
development and validation of an lc–ms/ms method for quantification of nc-8 in rat plasma and its application to pharmacokinetic studies |
publisher |
Elsevier |
series |
Journal of Food and Drug Analysis |
issn |
1021-9498 |
publishDate |
2018-01-01 |
description |
ent-16-Oxobeyeran-19-N-methylureido (NC-8) is a recently synthesized derivative of isosteviol that showed anti-hepatitis B virus (HBV) activity by disturbing replication and gene expression of the HBV and by inhibiting the host toll-like receptor 2/nuclear factor-κB signaling pathway. To study its pharmacokinetics as a part of the drug development process, a highly sensitive, rapid, and reliable liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed and validated for determining NC-8 in rat plasma. After protein precipitation extraction, the chromatographic separation of the analyte and internal standard (IS; diclofenac sodium) was performed on a reverse-phase Luna C18 column coupled with a Quattro Ultima triple quadruple mass spectrometer in the multiple-reaction monitoring mode using the transitions, m/z 347.31 → 75.09 for NC-8 and m/z 295.89 → 214.06 for the IS. The lower limit of quantitation was 0.5 ng/mL. The linear scope of the standard curve was between 0.5 and 500 ng/mL. Both the precision (coefficient of variation; %) and accuracy (relative error; %) were within acceptable criteria of <15%. Recoveries ranged from 104% to 113.4%, and the matrix effects (absolute) were non-significant (CV ≤ 6%). The validated method was successfully applied to investigate the pharmacokinetics of NC-8 in male Sprague–Dawley rats. The present methodology provides an analytical means to better understand the preliminary pharmacokinetics of NC-8 for investigations on further drug development. |
topic |
Isosteviol derivative LC–MS/MS NC-8 Pharmacokinetics |
url |
http://www.sciencedirect.com/science/article/pii/S1021949817301825 |
work_keys_str_mv |
AT baxterhepburnkachingwe developmentandvalidationofanlcmsmsmethodforquantificationofnc8inratplasmaanditsapplicationtopharmacokineticstudies AT yowshienguang developmentandvalidationofanlcmsmsmethodforquantificationofnc8inratplasmaanditsapplicationtopharmacokineticstudies AT tsurngjuhnhuang developmentandvalidationofanlcmsmsmethodforquantificationofnc8inratplasmaanditsapplicationtopharmacokineticstudies AT lihsuanwang developmentandvalidationofanlcmsmsmethodforquantificationofnc8inratplasmaanditsapplicationtopharmacokineticstudies AT shwujiuanlin developmentandvalidationofanlcmsmsmethodforquantificationofnc8inratplasmaanditsapplicationtopharmacokineticstudies |
_version_ |
1716748780882100224 |