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Updated: Aug 15, 2026
High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry
Published on: April 23, 2019
Development and Validation of an HPLC-MS/MS Method for Determining BMS-1166, GB-1107, and Enzalutamide in Rat Plasma
Shengnan Wang1, Shijia Lu2, Guofei Li2
1Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, People's Republic of China.
Purpose:
Hepatocellular carcinoma (HCC) is a highly lethal malignancy with poor prognosis and limited clinical treatments. CD8⁺ T cell-based immunotherapy offers promising therapeutic potential against HCC. We fabricated MMP-9/pH dual-sensitive liposomes co-encapsulating enzalutamide, GB-1107 and BMS-1166 for HCC treatment. Reliable detection approaches are lacking to assess in vivo liposomal behavior. This study established an HPLC-MS/MS method for simultaneous determination of the three drugs in rat plasma, and applied it to characterize their pharmacokinetic profiles.
Methods:
The pH/MMP-9 dual-sensitive liposomes co-loaded with BMS-1166, GB-1107 and enzalutamide were prepared via the thin-film hydration method, and the resultant formulations exhibited satisfactory pharmaceutical properties meeting the predefined quality criteria. For chromatographic separation, a poroshell 120 EC-C18 column (50 × 4.6 mm, 2.7 μm) was adopted, combined with linear gradient elution of 0.1% formic acid in water and acetonitrile. Full validation of the established method was performed strictly following the guidelines for bioanalytical method validation as stated in the Chinese Pharmacopoeia.
Results:
BMS-1166, GB-1107, and enzalutamide exhibited good linearity over the concentration range of 1.0-1000.0 ng/mL. The accuracy and precision of BMS-1166, GB-1107, and enzalutamide all fall below 11.1%. In addition, the recoveries and matrix effect for these analytes ranged from 88.6%-99.7%. Pharmacokinetic results demonstrated that the prepared liposomes possessed favorable in vivo long-circulating properties, which prolonged the half-lives of BMS-1166 and GB-1107 by 25-fold and 13-fold, respectively, and enhanced their bioavailability by 35-fold and 30-fold, respectively. In contrast, no statistically significant effect was observed on enzalutamide.
Conclusion:
The established method was validated and met the predefined quality criteria, thereby being suitable for investigating the in vivo pharmacokinetic profiles of BMS-1166, GB-1107, and enzalutamide.
