| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1212252 | Journal of Chromatography B | 2015 | 7 Pages |
•In this study, a sensitive, rapid and high-throughput quantitative bioanalytical method has been established by using 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. We utilized this HPLC–MS/MS method to analyze the distribution difference of bromocriptine in post-operative responsive and non-responding prolactinomas. Finally we have found that bromocriptine concentration in non-responding prolactinomas was significantly higher than that in sensitive prolactinomas, and confirmed that the failure of bromocriptine treatment in non-responding patients with prolactinoma was “intrinsic” tumor (cell) resistence, rather than insufficient drug concentration in tumor tissue.
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.
