TY - JOUR
T1 - A stability indicating LC-MS/MS method for quantification of a NOX Inhibitor R14 in its bisulfite adduct form for pharmacokinetic studies
AU - Wang, Yang
AU - Ma, Jing
AU - Lin, Shiaw Yih
AU - Xie, Huan
AU - Liang, Dong
N1 - Funding Information:
This study was funded in part by the Cancer Prevention & Research Institute of Texas ( CPRIT ) Core Facilities Support Awards ( RP180748 ), the NIH/NIMHD-Research Centers in Minority Institutions Program ( U54MD007605 ) to D.L. and H.X., and NCI R01CA251206 to S-YL.
Publisher Copyright:
© 2023
PY - 2023/5/10
Y1 - 2023/5/10
N2 - R14, also known as NOX Inhibitor VII, is a potent inhibitor of NADPH oxidases (NOX) which has recently been identified as a novel agent targeting to triple-negative breast cancer. It is also rapidly degraded in collected pharmacokinetic plasma and blood samples even stored under − 70 °C. The purpose of this study was to develop a stability indicating LC-MS/MS assay that would be suitable for quantification of R14 in plasma and blood. In the presence of sodium sulfite under acidic pH, R14, an aryl lactam compound which is not a typically reactive compound for bisulfite addition, readily and completely converted to R14 bisulfite adduct, which was more stable in plasma and blood. The adduct has MRM transition at m/z 340.1–127.0 in negative mode and showed high sensitivity in LC-MS/MS quantification. Thus, monitoring the adduct provided a suitable way of quantitating R14 concentrations in mouse whole blood. The reacting conditions were optimized based on detecting R14 bisulfite adduct, and the assay was established and validated on a SCIEX 6500+ Triple Quad LC-MS/MS System. The method was then successfully adapted to pharmacokinetic studies after oral administration of R14 to mice.
AB - R14, also known as NOX Inhibitor VII, is a potent inhibitor of NADPH oxidases (NOX) which has recently been identified as a novel agent targeting to triple-negative breast cancer. It is also rapidly degraded in collected pharmacokinetic plasma and blood samples even stored under − 70 °C. The purpose of this study was to develop a stability indicating LC-MS/MS assay that would be suitable for quantification of R14 in plasma and blood. In the presence of sodium sulfite under acidic pH, R14, an aryl lactam compound which is not a typically reactive compound for bisulfite addition, readily and completely converted to R14 bisulfite adduct, which was more stable in plasma and blood. The adduct has MRM transition at m/z 340.1–127.0 in negative mode and showed high sensitivity in LC-MS/MS quantification. Thus, monitoring the adduct provided a suitable way of quantitating R14 concentrations in mouse whole blood. The reacting conditions were optimized based on detecting R14 bisulfite adduct, and the assay was established and validated on a SCIEX 6500+ Triple Quad LC-MS/MS System. The method was then successfully adapted to pharmacokinetic studies after oral administration of R14 to mice.
KW - Bisulfite adduct
KW - LC-MS/MS
KW - NOX Inhibitor R14
KW - Pharmacokinetic study
UR - http://www.scopus.com/inward/record.url?scp=85149891765&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85149891765&partnerID=8YFLogxK
U2 - 10.1016/j.jpba.2023.115326
DO - 10.1016/j.jpba.2023.115326
M3 - Article
C2 - 36924633
AN - SCOPUS:85149891765
SN - 0731-7085
VL - 228
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
M1 - 115326
ER -