Mycophenolic acid (MPA) has being used clinically for organ rejection prophylaxis. Recent studies have revealed that MPA can also act as a chemo-sensitizing agent when used in combination with various chemotherapeutic agents in a cancer type-specific manner, including with oxaliplatin on oral squamous cell carcinoma (OSCC) cells. To prepare for the analysis of a novel drug delivery route for MPA absorption via oral mucosa as a potential therapeutic product, it is essential to develop and validate a highly sensitive analytical method for the quantification of MPA in biological samples for pharmacokinetic and tissue distribution studies. Herein, we report a sensitive, specific and reproducible UPLC-MS/MS method to do so. Blank rat plasma or tongue tissue homogenates coupled with griseofulvin, as internal standard, was used for generating standard curves ranging from 0.5 to 1000 ng/mL (r > 0.9990) for both plasma and tongue tissue homogenates. The chromatographic separation was achieved by a reverse phase ACE Excel 2 Super C18 column with a flow rate of 0.4 mL/min under gradient elution. Mass detection was performed under positive ionization electrospray. Inter- and intra-day accuracy and precision of the assay were ≤15% in both plasma and tongue tissue homogenates. The matrix effect was non-significant and extraction recovery rates were within 87.99% and 109.69% in plasma and tongue homogenates, respectively. The validity of this assay has been confirmed by measuring MPA in rat plasma for pharmacokinetics following intravenous administration of 0.5 mg/kg of mycophenolate sodium, as well as monitoring MPA in rat tongues for tissue distribution and detecting MPA that diffused into systemic circulation following a 4-h transmucosal delivery of 357 μg/cm2 of mycophenolate sodium.

中文翻译：

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通过UPLC-MS / MS方法测定和验证麦考酚酸：在大鼠药代动力学和舌组织分布研究中的应用。

麦考酚酸（MPA）已在临床上用于预防器官排斥。最近的研究表明，MPA还可以与多种化学治疗剂以癌症类型特异性的方式结合使用，包括奥沙利铂对口腔鳞状细胞癌（OSCC）细胞的化学增敏剂。为了准备分析通过口腔粘膜作为潜在治疗产品吸收MPA的新药物递送途径的分析，必须开发和验证一种高度灵敏的分析方法，用于定量生物样品中MPA的药代动力学和组织分布研究。在此，我们报告了一种灵敏，特异且可重现的UPLC-MS / MS方法。空白大鼠血浆或舌组织匀浆再加上灰黄霉素，作为内标，用于血浆和舌头组织匀浆的标准曲线的生成范围为0.5至1000 ng / mL（r> 0.9990）的标准曲线。通过反相ACE Excel 2 Super C18色谱柱在梯度洗脱下以0.4 mL / min的流速进行色谱分离。在正电离电喷雾下进行质量检测。在血浆和舌头组织匀浆中，日间和日间测定的准确性和精密度均≤15％。血浆和舌头匀浆的基质效应不显着，提取回收率分别在87.99％和109.69％之内。静脉注射0.5 mg / kg的麦考酚酸钠后，通过测量大鼠血浆中MPA的药代动力学，已证实了该测定法的有效性，