Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box No.2457 Riyadh, Saudi Arabia; Bioavailability Laboratory, College of Pharmacy, King Saud University, PO Box No.2457 Riyadh, Saudi Arabia.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box No.2457 Riyadh, Saudi Arabia; Bioavailability Laboratory, College of Pharmacy, King Saud University, PO Box No.2457 Riyadh, Saudi Arabia.
J Pharm Biomed Anal. 2018 Feb 5;149:172-178. doi: 10.1016/j.jpba.2017.10.024. Epub 2017 Oct 28.
Eluxadoline is a novel μ- and κ-opioid receptor (OR) agonist and δ-OR antagonist, recently approved as a first line therapy for the treatment of irritable bowel syndrome. Due to abuse potential, poor bioavailability and high intersubject variability, a sensitive and reliable assay is prerequisite for its determination in biological samples. This work first time report the development and validation of UPLC-MS/MS assay for determination of eluxadoline in rat plasma sample using risperidone as an internal standard (IS). A high-throughput 96-well plate format μ-SPE technique was used for plasma sample extraction. The extracted samples were separated on Acquity BEH™ C column (100×2.1mm, 1.7μm) using mobile phase elution of acetonitrile: 20mM ammonium acetate (80:20, v/v) at a flow rate of 0.3mLmin. The precursor to product ion transition of m/z 570.16→118.12 (qualifier), 570.16→171.08 (quantifier) for eluxadoline, and m/z 411.18→191.07 for IS were used for MRM monitoring. The calibration curves were linear in concentration range of 0.15-50ngmL with LOD and LOQ of 0.07 and 0.15ngmL, respectively. The validation results satisfied the criteria of USFDA and SWGTOX guidelines and were within the acceptable limit. Finally, the method was successfully applied in bioavailability enhancement study of the newly developed PLGA nanoparticles and Eudragit coated PLGA nanoparticles of eluxadoline in rats.
埃卢索多林是一种新型 μ 和 κ 阿片受体（OR）激动剂和 δ-OR 拮抗剂，最近被批准为治疗肠易激综合征的一线治疗药物。由于滥用潜力、生物利用度差和个体间变异性高，因此需要一种灵敏可靠的测定方法来测定生物样品中的埃卢索多林。本工作首次报道了采用利培酮作为内标（IS），用超高效液相色谱-串联质谱法（UPLC-MS/MS）测定大鼠血浆中埃卢索多林的方法开发和验证。采用高通量 96 孔板格式的 μ-SPE 技术进行血浆样品提取。提取的样品在 Acquity BEH™ C 柱（100×2.1mm，1.7μm）上进行分离，以乙腈：20mM 乙酸铵（80:20，v/v）为流动相洗脱，流速为 0.3mLmin。用于 MRM 监测的母离子-子离子转换为 m/z 570.16→118.12（定性）、m/z 570.16→171.08（定量）（定量）。埃卢索多林和 m/z 411.18→191.07（定量）为 IS。校准曲线在浓度范围为 0.15-50ngmL 时呈线性，LOD 和 LOQ 分别为 0.07 和 0.15ngmL。验证结果符合美国 FDA 和 SWGTOX 指南的标准，且在可接受范围内。最后，该方法成功应用于新开发的埃卢索多林 PLGA 纳米粒和 Eudragit 包衣 PLGA 纳米粒的生物利用度增强研究。
