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Liquid chromatography tandem mass spectrometry method for determination of fulvestrant in rat plasma and its application to pharmacokinetic studies of a novel fulvestrant microcrystal
Author(s) -
Leng Guangyi,
Zuo Yanhua,
Hu Jiahui,
Yu Fei,
Liu Wanhui
Publication year - 2020
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4912
Subject(s) - fulvestrant , chemistry , chromatography , pharmacokinetics , tandem mass spectrometry , liquid chromatography–mass spectrometry , mass spectrometry , pharmacology , estrogen receptor , cancer , breast cancer , medicine
Fulvestrant (‘Faslodex’), an estrogen receptor antagonist, is available for the treatment of advanced breast cancer. The oil‐based vehicle of Faslodex can lead to various adverse effects. A novel fulvestrant microcrystal (aqueous suspension) was developed in this study to eliminate these adverse effects. A sensitive and robust liquid chromatography tandem mass spectrometry method was developed and validated for the determination of fulvestrant in rat plasma using supported‐liquid extraction. The separation of fulvestrant was achieved on an Agilent SB‐C 18 column (2.1 × 50 mm, 3.5 μm) with isocratic elution using fulvestrant‐d3 as internal standard. Mass spectrometric detection was conducted in negative multiple reaction monitoring mode. Ion transitions were at m/z 605.5 → 427.5 for fulvestrant and m/z 608.5 → 430.5 for fulvestrant‐d3. The excellent linearity was demonstrated over the range 0.05–100.0 ng/ml ( r 2 = 0.99). The lower limit of quantitation was 0.05 ng/ml, which was superior to that reported in literature The method validation was evaluated by selectivity, accuracy, precision, recovery and matrix effect in agreement with the US Food and Drug Administration guidance. The method was successfully applied to a pharmacokinetic study of a novel fulvestrant microcrystal in rats after intramuscular administration. It revealed that the rate of absorption increases and the extent of absorption is constant with a decrease in microcrystal diameter.