Development and validation of a liquid chromatography-mass spectrometry assay for quantification of Z- and E- isomers of endoxifen and its metabolites in plasma from women with estrogen receptor positive breast cancer

•Few methods exist to identify and quantify endoxifen metabolites.•Developed a LC-MS/MS method for identification and quantification of endoxifen metabolites.•Method was validated and determined to be rapid, sensitive, and specific.•Method was successfully applied to patient plasma samples. The sele...

Full description

Saved in:
Bibliographic Details
Published in:Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2023-04, Vol.1221, p.123654-123654, Article 123654
Main Authors: Buhrow, Sarah A., Koubek, Emily J., Goetz, Matthew P., Ames, Matthew M., Reid, Joel M.
Format: Article
Language:English
Subjects:
Breast Neoplasms - drug therapy
Chromatography, High Pressure Liquid - methods
Chromatography, Liquid - methods
Endoxifen
Female
Humans
LC-MS/MS
Metabolite
Receptors, Estrogen - therapeutic use
Reproducibility of Results
Tamoxifen
Tandem Mass Spectrometry - methods
Validation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•Few methods exist to identify and quantify endoxifen metabolites.•Developed a LC-MS/MS method for identification and quantification of endoxifen metabolites.•Method was validated and determined to be rapid, sensitive, and specific.•Method was successfully applied to patient plasma samples. The selective estrogen receptor modifier tamoxifen (TAM) is widely used for the treatment of women with estrogen receptor positive (ER+ ) breast cancer. Endoxifen (ENDX) is a potent, active metabolite of TAM and is important for TAM’s clinical activity. While multiple papers have been published regarding TAM metabolism, few studies have examined or quantified the metabolism of ENDX. To quantify ENDX and its metabolites in patient plasma samples, we have developed and validated a rapid, sensitive, and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative determination of the E- and Z-isomers of ENDX (0.5–500 ng/ml) and the ENDX metabolites norendoxifen (1–500 and 0.5–500 ng/ml E and Z, respectfully), ENDX catechol (3.075–307.5 and 1.92–192 ng/ml E and Z, respectfully), 4′-hydroxy ENDX (0.33–166.5 and 0.33–333.5 ng/ml E and Z, respectfully), ENDX methoxycatechol (0.3–300 and 0.2–200 ng/ml E and Z, respectfully), and ENDX glucuronide (2–200 and 3–300 ng/ml E and Z, respectfully) in human plasma. Chromatographic separation was accomplished on a HSS T3 precolumn attached to an Poroshell 120 EC-C18 analytical column using 0.1 % formic acid/water and 0.1 % formic acid/methanol as eluents followed by MS/MS detection. The analytical run time was 6.5 min. Standard curves were linear (R2 ≥ 0.98) over the concentration ranges. The intra- and inter-day precision and accuracy, determined at high-, middle-, and low-quality control concentrations for all analytes, were within the acceptable range of 85 % and 115 %. The average percent recoveries were all above 90 %. The method was successfully applied to clinical plasma samples from a Phase I study of daily oral Z-ENDX.
ISSN:1570-0232
1873-376X
DOI:10.1016/j.jchromb.2023.123654