Determination of eldecalcitol in human plasma by SIL-IS UPLC-APCI-MS/MS method for pharmacokinetics study

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS Journal of Chromatography B Pub Date : 2025-02-01 DOI:10.1016/j.jchromb.2025.124468

Wanyu Wang , Zhichao Yin , Pengfei Du , Jianbang Wu , Minhui Wang , Yaqin Wang , Ping Wu , Xiaocui Xia , Lin Zhang , Yamin Liu , Zhenyue Gao , Jie Shen , Yuanwei Jia

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Abstract

Eldecalcitol is a novel analog of 1α,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] for the treatment of patients with osteoporosis. A highly sensitive and specific ultra-performance liquid chromatography coupled to atmospheric pressure chemical ionization tandem mass spectrometry (UPLC-APCI-MS/MS) technique featuring a lower limit of quantitation (LLOQ) as low as 5 pg/ml, has been established and validated for the rapid and accurate quantification of eldecalcitol in human plasma samples. Plasma samples were extracted by solid phase extraction (SPE). Stable isotope-labeled compound eldecalcitol-d6 was used as an internal standard (SIL-IS). The detection process was carried out utilizing Multi-Reaction Monitoring (MRM) mode, employing an atmospheric pressure chemical ionization (APCI) source operating in the positive ion modality. The target fragment ion pairs for eldecalcitol and SIL-IS were identified as m/z 508.6 transitioning to 397.4, and m/z 514.6 transitioning to 403.3, respectively. This method was validated regarding selectivity, LLOQ, linearity, accuracy and precision, recovery, matrix effects, dilution reliability, stability, carryover test, and incurred sample reanalysis (ISR). This methodology had been successfully employed to assess the pharmacokinetics (PK) profile of eldecalcitol in a clinical investigation.

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SIL-IS UPLC-APCI-MS/MS法测定人血浆中艾尔地骨糖醇的药代动力学研究。

Eldecalcitol是一种新的类似于1α，25-二羟基维生素D3 [1,25(OH)2D3]的药物，用于治疗骨质疏松症。建立了一种高灵敏度、高特异性的超高效液相色谱-常压化学电离串联质谱（UPLC-APCI-MS/MS）技术，该技术的定量下限（LLOQ）低至5 pg/ml，可快速、准确地定量测定人血浆样品中的艾尔地钙醇。血浆样品采用固相萃取法（SPE）提取。采用稳定同位素标记化合物钙醇-d6作为内标（SIL-IS）。检测过程采用多反应监测（MRM）模式，采用正离子模式的常压化学电离（APCI）源。eldecalcitol和SIL-IS的目标片段离子对分别为m/z 508.6向397.4过渡，m/z 514.6向403.3过渡。对该方法进行了选择性、定量限、线性度、准确度和精密度、回收率、基质效应、稀释度可靠性、稳定性、遗留试验和引起的样品再分析（ISR）等方面的验证。该方法已在临床研究中成功地用于评估依地骨糖醇的药代动力学（PK）特征。

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来源期刊

Journal of Chromatography B 医学-分析化学

CiteScore

5.60

自引率

3.30%

发文量

306

审稿时长

44 days

期刊介绍： The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis. Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches. Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.