Department of Chemistry - Biomedical Center, Analytical Chemistry and Neurochemistry, Uppsala University, Uppsala, Sweden.
Innovation and Development Department, Fresenius-Kabi, Uppsala, Sweden.
Anal Methods. 2023 May 25;15(20):2480-2489. doi: 10.1039/d3ay00407d.
Evaluating total parenteral nutrition (TPN) products for quality assurance and quality control is crucial due to the chemical complexity of its components. With the advent of exploring different approaches for analysing TPN components using tandem mass spectrometry techniques, there is still a need for a robust and reproducible method for industrial routine analyses. This study allows simple, simultaneous determination of 22 fatty acids (FAs) commonly found in TPN components using gas chromatography-mass spectrometry (GC-MS). Five different transesterification techniques were applied for the FA standards and the sodium methoxide in methanol-dimethyl carbonate method was selected due to its good methylation efficiency. Fatty acid methyl esters (FAMEs) were separated in gas chromatography using an HP-5MS UI column with helium as the carrier gas. Mass spectrometry was used to fragment and quantify FAMEs using electron ionization (EI) and selected ion monitoring (SIM) mode. The analytical method was evaluated using the guidelines from the US Food and Drug Agency (FDA) and European Medicines Agency (EMA) in compliance with the International Council for Harmonization (ICH) document Q2(R2). Correlation coefficients () of the calibration curves for FAMEs were 0.99, except for C24:1 n-9 and C24:0, both = 0.98. The limits of detection (LOD) and quantification (LOQ) were found to be 1.69 μg mL and 5.14 μg mL, respectively. The linear range was from 3.10-179.9 μg mL for most FAMEs, except for C18:1 n-7 (3.96-224.9 μg mL) and C18:1 n-9 (6.30-349.57 μg mL). The intra-day and inter-day precision coefficients of variance (CV) of the method were less than 11.10% and 11.30%, respectively. Freeze-thaw cycles and ambient temperature measurements were performed for assessing sample stability. The validated method was applied to analyse major TPN components-fish and olive oils, and an unidentified lipid sample. The presented GC-MS method is simple and robust in the identification and quantification of 22 fatty acids simultaneously in the tested TPN components.
评估全肠外营养（TPN）产品的质量保证和质量控制至关重要，因为其成分的化学复杂性。随着探索使用串联质谱技术分析 TPN 成分的不同方法的出现，仍然需要一种用于工业常规分析的稳健且可重复的方法。本研究允许使用气相色谱-质谱联用（GC-MS）简单、同时测定 TPN 成分中常见的 22 种脂肪酸（FA）。应用了五种不同的酯交换技术来测定 FA 标准，甲醇-碳酸二甲酯中的甲醇钠方法由于其良好的甲基化效率而被选择。脂肪酸甲酯（FAMEs）在气相色谱中使用 HP-5MS UI 柱，以氦气作为载气进行分离。质谱法用于通过电子电离（EI）和选择离子监测（SIM）模式对 FAMEs 进行片段化和定量。该分析方法按照美国食品和药物管理局（FDA）和欧洲药品管理局（EMA）的指南进行评估，符合国际协调会议（ICH）文件 Q2(R2)。FAMEs 的校准曲线的相关系数（r）均为 0.99，除了 C24:1 n-9 和 C24:0，均为 0.98。检测限（LOD）和定量限（LOQ）分别为 1.69 μg mL 和 5.14 μg mL。大多数 FAMEs 的线性范围为 3.10-179.9 μg mL，除了 C18:1 n-7（3.96-224.9 μg mL）和 C18:1 n-9（6.30-349.57 μg mL）。该方法的日内和日间精密度变异系数（CV）均小于 11.10%和 11.30%。进行了冻融循环和环境温度测量，以评估样品稳定性。所验证的方法应用于分析主要的 TPN 成分-鱼油和橄榄油，以及一个未识别的脂质样品。所提出的 GC-MS 方法简单、稳健，可同时对测试的 TPN 成分中的 22 种脂肪酸进行鉴定和定量。
