College of Pharmacy, Dankook University, Cheonan, Chungnam, 31116, South Korea.
Arch Pharm Res. 2016 Dec;39(12):1653-1662. doi: 10.1007/s12272-016-0845-2. Epub 2016 Oct 17.
Osteoarthritis (OA) is the most common type of arthritis. To manage OA, in general, oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) is used. Recently, the analgesic and anti-inflammatory efficacy of piroxicam (PX), a long-acting NSAID, by intra-articular (IA) administration in OA was reported, and the possibility that PX is distributed in articular tissues at a certain concentration was raised. Thus, herein, novel LC-MS/MS methods to detect PX in rat articular tissue and plasma are presented. For articular tissue, solvent extraction with acetonitrile for 12 h was employed and a protein precipitation method was used for the preparation of a plasma sample. The developed methods were validated by following the FDA guidelines, and the validated methods were successfully applied to a PK study of IA PX. The present study presents, to our knowledge, the first method of determining a drug in articular tissue. Additionally, the level of PX in articular tissue after IA PX administration was experimentally confirmed for the first time using the present methods. Therefore, the present methods provide a new direction for in vivo evaluation for IA PX formulations and contribute to the development of alternative IA PX formulations with better effects for the treatment of OA.
骨关节炎（OA）是最常见的关节炎类型。为了治疗 OA，一般采用口服非甾体抗炎药（NSAIDs）。最近，有报道称，长效 NSAIDs 吡罗昔康（PX）通过关节内（IA）给药在 OA 中具有镇痛和抗炎作用，并提出了 PX 以一定浓度分布在关节组织中的可能性。因此，本文提出了用于检测大鼠关节组织和血浆中 PX 的新型 LC-MS/MS 方法。对于关节组织，采用乙腈 12 小时溶剂提取，并采用蛋白沉淀法制备血浆样品。该方法按照 FDA 指南进行了验证，所建立的方法成功地应用于 IA PX 的 PK 研究。据我们所知，本研究首次提出了一种用于检测关节组织中药物的方法。此外，本研究首次使用该方法实验性地证实了 IA PX 给药后关节组织中 PX 的水平。因此，本方法为 IA PX 制剂的体内评价提供了新的方向，并有助于开发治疗 OA 效果更好的替代 IA PX 制剂。
