TY - JOUR
T1 - Determination and disposition of meta-iodobenzylguanidine in plasma and heart of transporter-deficient mice by UPLC-MS/MS
AU - Talebi, Zahra
AU - Jin, Yan
AU - Baker, Sharyn D.
AU - Addison, Daniel
AU - Sparreboom, Alex
N1 - Funding Information:
This project was supported in part by NIH grants P30CA016058 and U24CA247648, and the OSU Comprehensive Cancer Center Pelotonia foundation.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/4/1
Y1 - 2023/4/1
N2 - A simple LC-MS/MS method for the quantitative determination of the norepinephrine analogue meta-iodobenzyl-guanidine (mIBG) was developed and validated for mouse plasma and tissues, including salivary gland and heart. The assay procedure involved a one-step solvent extraction of mIBG and the internal standard N-(4-fluorobenzyl)-guandine from plasma or tissue homogenates with acetonitrile. An Accucore aQ column was used to separate analytes using a gradient elution with a total run time of 3.5 min. Validation studies with quality control samples processed on consecutive days revealed values for intra-day and inter-day precision of < 11.3%, with values for accuracy ranging 96.8–111%. Linear responses were observed over the entire calibration curves range (up to 100 ng/mL), and the lower limit of quantification was 0.1 ng/mL, using sample volumes of 5 µL. The developed method was successfully applied to evaluate the plasma pharmacokinetics and tissue distribution of mIBG in wild-type mice and animals lacking the organic cation transporters OCT1, OCT2, OCT3, and/or MATE1 to further understand mechanisms contributing to drug distribution and elimination and causes of inter-individual pharmacokinetic variability.
AB - A simple LC-MS/MS method for the quantitative determination of the norepinephrine analogue meta-iodobenzyl-guanidine (mIBG) was developed and validated for mouse plasma and tissues, including salivary gland and heart. The assay procedure involved a one-step solvent extraction of mIBG and the internal standard N-(4-fluorobenzyl)-guandine from plasma or tissue homogenates with acetonitrile. An Accucore aQ column was used to separate analytes using a gradient elution with a total run time of 3.5 min. Validation studies with quality control samples processed on consecutive days revealed values for intra-day and inter-day precision of < 11.3%, with values for accuracy ranging 96.8–111%. Linear responses were observed over the entire calibration curves range (up to 100 ng/mL), and the lower limit of quantification was 0.1 ng/mL, using sample volumes of 5 µL. The developed method was successfully applied to evaluate the plasma pharmacokinetics and tissue distribution of mIBG in wild-type mice and animals lacking the organic cation transporters OCT1, OCT2, OCT3, and/or MATE1 to further understand mechanisms contributing to drug distribution and elimination and causes of inter-individual pharmacokinetic variability.
KW - Mouse plasma and heart
KW - Pharmacokinetics
KW - UPLC-MS/MS
KW - mIBG
UR - http://www.scopus.com/inward/record.url?scp=85152614813&partnerID=8YFLogxK
U2 - 10.1016/j.jchromb.2023.123699
DO - 10.1016/j.jchromb.2023.123699
M3 - Article
C2 - 37059009
AN - SCOPUS:85152614813
SN - 1570-0232
VL - 1222
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
M1 - 123699
ER -