title: A sensitive and rapid HPLC-MS/MS method for the quantitative determination of trace amount of bromocriptine in small clinical prolactinoma tissue.
abstract: Usually, insufficient intratumoral concentration of therapeutic drugs is one of the reasons for tumor treatment failure. However, little is known about intratumoral distribution of bromocriptine in non-responding prolactinomas because of extremely low drug concentration and small prolactinoma tissue samples. In this study, a sensitive, rapid and high-throughput quantitative bioanalytical method has been established by using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for the determination of bromocriptine at trace level in human prolactinoma tissue. As little as 20 mg (wet weight) tissue sample was required and total analysis time was 6 min in this method. The assay quantifies over a linear range of 50 fg/mg to 5 pg/mg, and has a 25 fg/mg limit of detection at a signal/noise ratio of 3. This validated method was successfully used to quantitatively determine bromocriptine in clinical post-operative bromocriptine-sensitive and -resistant prolactinomas. The results revealed bromocriptine concentration in resistant prolactinomas (0.49-1.25 pg/mg) was significantly higher than that in sensitive prolactinomas (0.057-0.47 pg/mg). These results provided direct evidence to demonstrate the reseaon for failure of bromocriptine treatment in some patients with prolactinoma was "intrinsic" tumor (cell) resistence, rather than insufficient drug concentration in tumor tissue. Additionaly, this HPLC-MS/MS method has been shown to be suitable for bromocriptine analysis in small amount tissue sample and could be adapted for therapeutic drug monitoring of other clinical medicine.
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors: Qingce
authors: Q
authors: Zang
authors: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China.
authors: Yang
authors: Y
authors: Liu
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors: Jiuming
authors: J
authors: He
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors: Xiaofei
authors: X
authors: Yue
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
authors: Ruiping
authors: R
authors: Zhang
authors: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China.
authors: Renzhi
authors: R
authors: Wang
authors: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China. Electronic address: zeper@imm.ac.cn.
authors: Zeper
authors: Z
authors: Abliz
mesh_terms: D001971:Bromocriptine / Q000008:administration & dosage / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000032:analysis*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D010911:Pituitary Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D015175:Prolactinoma / Q000737:chemistry / Q000188:drug therapy*; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D018491:Dopamine Agonists; D001971:Bromocriptine
keywords: Bromocriptine; Drug resistance; HPLC–MS/MS; Prolactinoma; Quantitative analytical method