Erarpat Sezin, Bodur Süleyman, Öner Miray, Günkara Ömer Tahir, Bakırdere Sezgin
Faculty of Art and Science, Chemistry Department, Yıldız Technical University, İstanbul, Turkey.
Turkish Academy of Sciences (TÜBA), Ankara, Turkey.
Rapid Commun Mass Spectrom. 2022 Jun 30;36(12):e9282. doi: 10.1002/rcm.9282.
A derivatization switchable solvent liquid-liquid microextraction quadruple isotope dilution gas chromatography mass spectrometry (D-SS-LLME-ID -GC/MS) method is presented for the determination of hydroxychloroquine sulfate in human biofluids.
While mixing type/period and concentration of NaOH were optimized via a univariate optimization approach, a multivariate optimization approach was used to determine optimum values for relatively more important parameters such as volumes of derivatization agent (acetic anhydride), NaOH and switchable solvent.
Under the optimum experimental conditions, limit of detection and limit of quantification were calculated as 0.03 and 0.09 mg/kg (mass based), respectively. An isotopically labelled material (hydroxychloroquine methyl acetate-d ) was firstly synthesized to be used in ID experiments which give highly accurate and precise recovery results. After the application of D-SS-LLME-ID , superior percent recovery results were recorded as 99.9 ± 1.6-101.3 ± 1.2 for human serum, 99.9 ± 1.7-99.8 ± 1.8 for urine and 99.6 ± 1.5-101.0 ± 1.1 for saliva samples.
The developed D-SS-LLME-ID -GC/MS method compensates the complicated matrix effects of human biofluids and provides highly accurate quantification of an analyte with precise results.
本文提出了一种衍生化可切换溶剂液-液微萃取-四重同位素稀释气相色谱-质谱法（D-SS-LLME-ID -GC/MS）用于测定人体生物流体中的硫酸羟氯喹。
通过单变量优化方法对氢氧化钠的类型/周期和浓度进行优化，同时采用多变量优化方法确定相对更重要参数的最佳值，如衍生化试剂（乙酸酐）、氢氧化钠和可切换溶剂的体积。
在最佳实验条件下，检测限和定量限分别计算为0.03和0.09 mg/kg（基于质量）。首次合成了一种同位素标记物质（乙酸羟氯喹甲酯-d）用于同位素稀释实验，该实验给出了高度准确和精确的回收率结果。应用D-SS-LLME-ID后，人体血清的回收率结果优异，为99.9±1.6 - 101.3±1.2，尿液为99.9±1.7 - 99.8±1.8，唾液样本为99.6±1.5 - 101.0±1.1。
所开发的D-SS-LLME-ID -GC/MS方法补偿了人体生物流体复杂的基质效应，并提供了对分析物的高精度定量和精确结果。
