TY - JOUR
T1 - A validated HPLC-MS/MS method for the quantification of systemic mifepristone after subcutaneous application in mice
AU - Tevini, Julia
AU - Aminzadeh-Gohari, Sepideh
AU - Weber, Daniela D
AU - Catalano, Luca
AU - Stefan, Victoria E
AU - Redl, Elisa
AU - Herzog, Chiara
AU - Lang, Roland
AU - Widschwendter, Martin
AU - Felder, Thomas K
AU - Kofler, Barbara
N1 - Tevini, Aminzadeh-Gohari, Weber, Catalano, Stefan, Kofler:
Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria
Lang:
Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, Salzburg, Austria
Felder:
Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria
Institute of Pharmacy, Paracelsus Medical University, Salzburg, Austria
PY - 2024/8/8
Y1 - 2024/8/8
N2 - Mifepristone (RU486, MIF) is a synthetic steroidal hormone with progesterone and glucocorticoid receptor antagonistic characteristics. MIF is commonly used for pharmalogical abortions, but also for the treatment of endometrial and endocrine disorders. The goal of the study was to establish and validate a targeted HPLC-MS/MS method for the quantification of MIF and one of its active metabolites metapristone (MET) in plasma after subcutaneous implantation of slow-release MIF pellets in female BALB/c mice. Additionally, we aimed to apply the analytical method to tissue of several organs to understand the tissue-specific distribution of both analytes after release into systemic circulation. Sample preparation comprised a simple liquid-liquid extraction with diethylether and required 100 μl of plasma or homogenates of approximately 50 mg of tissue. The presented HPLC-MS/MS method showed high sensitivity with baseline separation of MIF, MET, and the internal standard levonorgestrel within a run time of only 8.0 minutes and comparable limits of quantification for plasma and tissue homogenates ranging from 40 pg ml-1 to 105 pg ml-1 for MIF and MET. The presented study is suitable for murine plasma and tissues and can be easily applied to human samples.
AB - Mifepristone (RU486, MIF) is a synthetic steroidal hormone with progesterone and glucocorticoid receptor antagonistic characteristics. MIF is commonly used for pharmalogical abortions, but also for the treatment of endometrial and endocrine disorders. The goal of the study was to establish and validate a targeted HPLC-MS/MS method for the quantification of MIF and one of its active metabolites metapristone (MET) in plasma after subcutaneous implantation of slow-release MIF pellets in female BALB/c mice. Additionally, we aimed to apply the analytical method to tissue of several organs to understand the tissue-specific distribution of both analytes after release into systemic circulation. Sample preparation comprised a simple liquid-liquid extraction with diethylether and required 100 μl of plasma or homogenates of approximately 50 mg of tissue. The presented HPLC-MS/MS method showed high sensitivity with baseline separation of MIF, MET, and the internal standard levonorgestrel within a run time of only 8.0 minutes and comparable limits of quantification for plasma and tissue homogenates ranging from 40 pg ml-1 to 105 pg ml-1 for MIF and MET. The presented study is suitable for murine plasma and tissues and can be easily applied to human samples.
U2 - 10.1039/d4ay00546e
DO - 10.1039/d4ay00546e
M3 - Original Article (Journal)
C2 - 39045617
SN - 1759-9660
VL - 16
SP - 5459
EP - 5466
JO - Analytical methods : advancing methods and applications
JF - Analytical methods : advancing methods and applications
IS - 31
ER -