Derivatization Strategies for the Detection of Triamcinolone Acetonide in Cartilage by Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging
Derivatization Strategies for the Detection of Triamcinolone Acetonide in Cartilage by Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging
复制标题
DOI：
10.1021/acs.analchem.6b02491
复制
发表时间：
2016-12-20
影响因子：
7.4
通讯作者：
Cillero-Pastor, Berta
中科院分区：
文献类型：
--
作者：
Barre, Florian P. Y.;Flinders, Bryn;Cillero-Pastor, Berta
以关节软骨组织变性为特征的骨性关节炎严重损害了全世界许多人的行动能力。退变被认为是由关节组织中发生的炎症过程介导的，包括软骨。关节腔内注射曲安奈德(TAA)是一种用于减轻骨性关节炎的炎症和疼痛的药物治疗方法。然而，TAA在无血管软骨中的渗透和分布还不是很清楚。我们利用基质辅助激光解吸/电离质谱仪(MALDI-MSI)直接监测药物在生物组织中的分布，评估TAA在体外孵育后在人软骨中的分布。不幸的是，TAA不容易被规则的电喷雾电离(ESI)或MALDI电离。为了解决这一问题，我们建立了一种组织上衍生化方法，用吉拉德试剂T(GIRT)在人培养的软骨中研究其分布并定量测定药物丰度(高达3.3ngMU L)。利用MALDI-MSI，我们的结果证实了一种皮质类固醇药物在人骨关节炎软骨中的渗透深度。
Osteoarthritis (OA), characterized by degeneration of the cartilaginous tissue in articular joints, severely impairs mobility in many people worldwide. The degeneration is thought to be mediated by inflammatory processes occurring in the tissue of the joint, including the cartilage. Intra-articular administered triamcinolone acetonide (TAA) is one of the drug treatments employed to ameliorate the inflammation and pain that characterizes OA. However, the penetration and distribution of TAA into the avascular cartilage is not well understood. We employed matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which has been previously used to directly monitor the distribution of drugs in biological tissues, to evaluate the distribution of TAA in human cartilage after in vitro incubation. Unfortunately, TAA is not easily ionized by regular electrospray ionization (ESI) or MALDI. To overcome this problem, we developed an on-tissue derivatization method with Girard's reagent T (GirT) in human incubated cartilage being able to study its distribution and quantify the drug abundance (up to 3.3 ng/mu L). Our results demonstrate the depth of penetration of a corticosteroid drug in human OA cartilage using MALDI-MSI.