학술논문
Simultaneous Quantification of Aromatase Inhibitors and Estrogens in Postmenopausal Breast Cancer Patients
Clinical Research Article
Clinical Research Article
Document Type
Academic Journal
Author
Source
Journal of Clinical Endocrinology & Metabolism. May 2022, Vol. 107 Issue 5, p1368, 7 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Breast cancer is the most common malignancy affecting women worldwide, and the leading cause of death among women in Europe in the age group of 30 to 59 years (1). [...]
Context: Currently there are no assays that can simultaneously quantify serum levels of the third-generation aromatase inhibitors (Als): letrozole, anastrozole, and exemestane, and the ultra-low levels of estrogens in postmenopausal breast cancer patients on Al treatment. Such measurements may be pivotal for the determination of optimal and individualized treatment regimens. We aimed at developing a liquid chromatography-tandem mass spectrometry (MS/MS) method for simultaneous assessment of letrozole, anastrozole, exemestane, and 17-hydroxyexemestane as well as subpicomolar levels of estradiol and estrone. Methods: Internal standards, calibrators, serum samples, and quality controls were in fully automated steps transferred to a deep-well plate for a 2-step liquid-liquid extraction. The extracts were reconstituted and analytes were separated chromatographically using 2 serially coupled columns, then subject to MS/MS in electrospray ionization mode. The method was thoroughly validated and is traceable to 2 accredited estrogen methods. Results: The measurement range for estrone and estradiol was 0.2 to 12 000 pmol/Land 0.8 to 13 000 pmol/L, and covered the expected therapeutic range for the Als. All analytes had a precision of less than or equal to 13%, and accuracies within 100 [+ or -] 8%. As proof of concept, Al and estrogen levels were determined in serum samples from postmenopausal breast cancer patients under treatment. Conclusion: We present here an assay suitable for the simultaneous measurement of serum levels of all third-generation Als and ultra-low evels of estrogens, providing a powerful new tool to study drug efficacy and compliance. The method is highly valuable for postmenopausal patients whose pretreatment estradiol levels are below the threshold of detection for most routine assays, but still require suppression. Key Words: estradiol, exemestane, letrozole, anastrozole, breast cancer, aromatase inhibitors
Context: Currently there are no assays that can simultaneously quantify serum levels of the third-generation aromatase inhibitors (Als): letrozole, anastrozole, and exemestane, and the ultra-low levels of estrogens in postmenopausal breast cancer patients on Al treatment. Such measurements may be pivotal for the determination of optimal and individualized treatment regimens. We aimed at developing a liquid chromatography-tandem mass spectrometry (MS/MS) method for simultaneous assessment of letrozole, anastrozole, exemestane, and 17-hydroxyexemestane as well as subpicomolar levels of estradiol and estrone. Methods: Internal standards, calibrators, serum samples, and quality controls were in fully automated steps transferred to a deep-well plate for a 2-step liquid-liquid extraction. The extracts were reconstituted and analytes were separated chromatographically using 2 serially coupled columns, then subject to MS/MS in electrospray ionization mode. The method was thoroughly validated and is traceable to 2 accredited estrogen methods. Results: The measurement range for estrone and estradiol was 0.2 to 12 000 pmol/Land 0.8 to 13 000 pmol/L, and covered the expected therapeutic range for the Als. All analytes had a precision of less than or equal to 13%, and accuracies within 100 [+ or -] 8%. As proof of concept, Al and estrogen levels were determined in serum samples from postmenopausal breast cancer patients under treatment. Conclusion: We present here an assay suitable for the simultaneous measurement of serum levels of all third-generation Als and ultra-low evels of estrogens, providing a powerful new tool to study drug efficacy and compliance. The method is highly valuable for postmenopausal patients whose pretreatment estradiol levels are below the threshold of detection for most routine assays, but still require suppression. Key Words: estradiol, exemestane, letrozole, anastrozole, breast cancer, aromatase inhibitors