TY - JOUR
T1 - Simultaneous determination and validation of oncrasin-266 and its metabolites by HPLC–MS/MS
T2 - Application to a pharmacokinetic study
AU - White, Lyndsey
AU - Wu, Shuhong
AU - Ma, Jing
AU - Fang, Bingliang
AU - Liang, Dong
N1 - Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/10/15
Y1 - 2016/10/15
N2 - Oncrasins are a class of RNA polymerase II inhibitors. Oncrasin-72 is an indole-3 carbinol analog that has shown to inhibit growth and induce the cell death of various human cancer cell lines. Oncrasin-266, a prodrug of oncrasin-72, has been shown to have improved pharmacokinetic properties and safety than Oncrasin-72. With respect to the potential therapeutic advantages of this class of compounds, there is a need for further preclinical assessment for future clinical trials. The development of and validation of an analytical method is essential for the quantification of oncrasins in biological fluids for pharmacokinetic studies. This study focuses on the HPLC–MS/MS method development and validation of oncrasin-266, oncrasin-72 and its aldehyde metabolite in rat plasma. Blank rat plasma, coupled with 1-(3-chlorobenzyl)-1H-indole, as internal standard, was used for generating standard curves ranging from 1 to 250 ng/mL for oncrasin-266 and oncrasin-72; and 0.5–125 ng/mL for the aldehyde metabolite. The chromatographic separation was achieved by a Zorbax 300SB-C18 HPLC column at 50°C with a flow rate of 1.1 mL/min under gradient elution. Mass detection was performed under positive ionization electrospray. Intra- and inter-day accuracy and precision of the assay were less than 10%. We report a simple, specific and reproducible HPLC–MS/MS method for the quantification of oncrasins in rat plasma. This study was successfully used for the quantification of oncrasins in rat plasma for pharmacokinetic studies in three dose groups of 10, 25, and 50 mg/kg via intravenous administration.
AB - Oncrasins are a class of RNA polymerase II inhibitors. Oncrasin-72 is an indole-3 carbinol analog that has shown to inhibit growth and induce the cell death of various human cancer cell lines. Oncrasin-266, a prodrug of oncrasin-72, has been shown to have improved pharmacokinetic properties and safety than Oncrasin-72. With respect to the potential therapeutic advantages of this class of compounds, there is a need for further preclinical assessment for future clinical trials. The development of and validation of an analytical method is essential for the quantification of oncrasins in biological fluids for pharmacokinetic studies. This study focuses on the HPLC–MS/MS method development and validation of oncrasin-266, oncrasin-72 and its aldehyde metabolite in rat plasma. Blank rat plasma, coupled with 1-(3-chlorobenzyl)-1H-indole, as internal standard, was used for generating standard curves ranging from 1 to 250 ng/mL for oncrasin-266 and oncrasin-72; and 0.5–125 ng/mL for the aldehyde metabolite. The chromatographic separation was achieved by a Zorbax 300SB-C18 HPLC column at 50°C with a flow rate of 1.1 mL/min under gradient elution. Mass detection was performed under positive ionization electrospray. Intra- and inter-day accuracy and precision of the assay were less than 10%. We report a simple, specific and reproducible HPLC–MS/MS method for the quantification of oncrasins in rat plasma. This study was successfully used for the quantification of oncrasins in rat plasma for pharmacokinetic studies in three dose groups of 10, 25, and 50 mg/kg via intravenous administration.
KW - LC–MS/MS
KW - Metabolite
KW - Oncrasin
KW - Pharmacokinetics
KW - Prodrug
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UR - http://www.scopus.com/inward/citedby.url?scp=84982135049&partnerID=8YFLogxK
U2 - 10.1016/j.jchromb.2016.07.033
DO - 10.1016/j.jchromb.2016.07.033
M3 - Article
C2 - 27541624
AN - SCOPUS:84982135049
SN - 1570-0232
VL - 1033-1034
SP - 106
EP - 111
JO - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
JF - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
ER -