Cromolyn sodium (CS) is a mast cell stabilizer administered to treat allergic diseases. A topical system would sustain its delivery and may be designed for treatment of atopic dermatitis. Established HPLC protocols for detection of CS are time consuming and intensive, indicating the need for a more streamlined method. This study aimed at developing and validating a sensitive and selective LC-MS method for quantifying CS in skin permeation studies that was less time and resource demanding. The optimized method involved an isocratic mobile phase (10 mM NH₄HCO₃, pH 8.0, 90% and ACN, 10%) at a flow rate of 0.25 mL/min. Detection involved direct MS/MS channels with m/z 467.0255 (precursor) and m/z 379.0517 (fragment) using argon as the collision gas. CS calibrants were prepared in PBS, pH 7.4, and methanol for validation (0.1–2.5 μg/mL). To ensure no skin interference, dermatomed porcine skin was mounted on Franz diffusion cells that were analyzed after 24 h. The skin layers were also separated, extracted in methanol, and analyzed using the developed method. Retention time was 1.9 min and 4.1 min in methanol and buffer, respectively. No interfering peaks were observed from the receptor and skin extracts, and linearity was established between 0.1 and 2.5 μg/mL. Interday and intraday accuracy and precision were within the acceptable limit of ±20% at the LLOQ and ±15% at other concentrations. Overall, the simplified, validated method showed sensitivity in detecting CS in skin without interference and was applied to demonstrate quantification of drug in skin following 4% cromolyn sodium gel exposure.

中文翻译：

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在皮肤渗透研究中测定色甘酸钠的液相色谱-质谱法的开发和验证

色甘酸钠 (CS) 是一种肥大细胞稳定剂，用于治疗过敏性疾病。局部系统将维持其递送，并可设计用于治疗特应性皮炎。已建立的用于检测 CS 的 HPLC 协议既费时又费力，这表明需要一种更简化的方法。本研究旨在开发和验证一种灵敏且选择性的 LC-MS 方法，用于在皮肤渗透研究中量化 CS，这种方法对时间和资源的要求较低。优化的方法涉及流速为 0.25 mL/min的等度流动相（10 mM NH ₄ HCO _{3 ，pH 8.0，90% 和 ACN，10%）。}检测涉及具有 m/z 467.0255（前体）和m / z的直接 MS/MS 通道379.0517（片段）使用氩气作为碰撞气体。CS 校准物在 PBS、pH 7.4 和甲醇中制备，用于验证 (0.1–2.5  μ g/mL)。为了确保没有皮肤干扰，将去皮的猪皮肤安装在 Franz 扩散池上，24 小时后对其进行分析。皮肤层也被分离，在甲醇中提取，并使用开发的方法进行分析。在甲醇和缓冲液中的保留时间分别为 1.9 分钟和 4.1 分钟。从受体和皮肤提取物中未观察到干扰峰，线性建立在 0.1 和 2.5  μ之间克/毫升。日间和日内准确度和精密度在 LLOQ 的 ±20% 和其他浓度的 ±15% 的可接受范围内。总体而言，简化的、经过验证的方法在检测皮肤中的 CS 时表现出灵敏度，而不会受到干扰，并用于证明暴露于 4% 色甘酸钠凝胶后皮肤中药物的定量。