Development of an HPLC-MS/MS Method for the Determination of Silybin in Human Plasma, Urine and Breast Tissue

Molecules

JoséAntonio Legarreta Iriberri¹  Digna Tost Robusté¹  Jaume Pascual Avellana¹  Sara Cagnacci²  Bernardo Bonanni²  Debora Macis²  Harriet Johansson²  Matteo Lazzeroni²  Valentina Aristarco²  Paolo Morazzoni³  Antonella Riva³  Giovanna Petrangolini³ 

[1] Bioanalysis Department, Kymos Pharma Services S.L., Ronda Can Fatjó 7-B, 08290 Cerdanyola del Vallès, Spain;IEO-European Institute of Oncology, Division of Cancer Prevention and Genetics, IRCCS, Via Ripamonti 435, 20141 Milan, Italy;Research and Development Department, Indena S.p.A., Viale Ortles 12, 20139 Milan, Italy;

关键词: silybin;    silibinin;    Siliphos^®;    breast cancer;    HPLC-MS/MS method;   

DOI  :  10.3390/molecules25122918

来源: DOAJ

【 摘 要 】

Silybin is a flavonolignan extracted from Silybum marianum with chemopreventive activity against various cancers, including breast. This study was designed to develop an HPLC-MS/MS method for the determination of silybin in human plasma, urine and breast tissue in early breast cancer patients undergoing Siliphos^® supplementation, an oral silybin-phosphatidylcholine complex. The determination of silybin was carried out by liquid–liquid extraction with methyl-tert-butyl ether (MTBE); total silybin concentration was determined by treating the samples with β–glucuronidase, while for the determination of free silybin, the hydrolytic step was omitted. Naringenin and naproxen were selected as internal standards. The detection of the analyte was carried out by mass spectrometry and by chromatography. The HPLC-MS/MS method was evaluated in terms of selectivity, linearity, limit of quantification, precision and accuracy, and carryover. The method proved to be selective, linear, precise and accurate for the determination of silybin. To the best of our knowledge, this presents the first analytical method with the capacity to quantify the major bioactive components of milk thistle in three different biological matrices with a lower limit of quantification of 0.5 ng/mL for plasma. Silybin phosphatidylcholine, taken orally, can deliver high blood concentrations of silybin, which selectively accumulates in breast tumor tissue.

【 授权许可】

Unknown