Chiral separation and quantitation of methylphenidate, ethylphenidate, and ritalinic acid in blood using supercritical fluid chromatography,Drug Testing and Analysis

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Chiral separation and quantitation of methylphenidate, ethylphenidate, and ritalinic acid in blood using supercritical fluid chromatography
Drug Testing and Analysis ( IF 2.6 ) Pub Date : 2023-01-24 , DOI: 10.1002/dta.3446
Christina Smith ₁ , Svante Vikingsson ₂ , Robert Kronstrand _{3,

4} , Madeleine J Swortwood ₁

Affiliation

Supercritical fluid chromatography (SFC) is a technique that analyzes compounds that are temperature-labile, have moderately low weight, or are chiral compounds. Methylphenidate (MPH) is a chiral compound with two chiral centers. MPH has two chiral metabolites, ethylphenidate (EPH) and ritalinic acid (RA). MPH is sold as a racemic mixture. The d-enantiomer of threo-MPH is responsible for medicinal effects. Due to the differing effects of the enantiomers, it is important to analyze the enantiomers individually to better understand their effects. This method utilizes SFCand solid-phase extraction (SPE) to separate and analyze the enantiomers of MPH, EPH, and RA in postmortem blood. The objective of this method was to assess a unique approach with SFC for enantiomeric separation of MPH, EPH, and RA. A SPE method was developed and optimized to isolate the analytes in blood and validated as fit-for-purpose following international guidelines. The linear range for MPH and EPH was 0.25–25 and 10–1000 ng/mL for RA in blood. Bias was −8.6% to 0.8%, and precision was within 15.4% for all analytes. Following method validation, this technique was applied to the analysis of 49 authentic samples previously analyzed with an achiral method. Quantitative results for RA were comparable to achiral technique, whereas there was loss of MPH and EPH over time. The l:d enantiomer ratio was calculated, and MPH demonstrated greater abundance of the d-enantiomer. This is the first known method to separate and quantify the enantiomers of all three analytes utilizing SFC and SPE.

中文翻译：

使用超临界流体色谱对血液中的哌醋甲酯、哌醋甲酯和利他林酸进行手性分离和定量

超临界流体色谱 (SFC) 是一种分析温度不稳定、重量适中或手性化合物的技术。哌醋甲酯 (MPH) 是一种具有两个手性中心的手性化合物。MPH 有两种手性代谢物，哌乙酯 (EPH) 和利他林酸 (RA)。MPH 作为外消旋混合物出售。苏式的d-对映体-MPH 负责药效。由于对映体的不同作用，单独分析对映体以更好地了解它们的作用非常重要。该方法利用 SFC 和固相萃取 (SPE) 分离和分析死后血液中 MPH、EPH 和 RA 的对映体。该方法的目的是评估使用 SFC 对 MPH、EPH 和 RA 进行对映体分离的独特方法。开发和优化了一种 SPE 方法，以分离血液中的分析物，并根据国际指南验证其适用性。血液中 RA 的 MPH 和 EPH 的线性范围为 0.25-25 和 10-1000 ng/mL。所有分析物的偏差为 -8.6% 至 0.8%，精密度在 15.4% 以内。方法验证后，该技术被应用于分析 49 个以前用非手性方法分析过的真实样品。RA 的定量结果与非手性技术相当，而 MPH 和 EPH 会随着时间的推移而损失。这计算了l:d对映异构体比率，MPH 证明了d-对映异构体的丰度更高。这是已知的第一种利用 SFC 和 SPE 分离和定量所有三种分析物的对映体的方法。

更新日期：2023-01-24

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