从干血斑中自动提取和定量免疫抑制剂和抗惊厥药:Transcend DBSA-TLX-1-MS /MS系统的评价

IF 1.3 4区 化学 Q4 BIOCHEMICAL RESEARCH METHODS
Pragya Sharma, Alison Lightfoot, Richard G. Lahr, Chris Thompson, Jennifer Faber, Joshua Miller, Jingshu Guo, Loralie J. Langman, Paul J. Jannetto, Anthony Maus
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引用次数: 0

摘要

免疫抑制剂和抗惊厥药物分别在全血和血清中常规使用液相色谱-串联质谱(LC-MS /MS)进行定量,这就需要经常对患者进行静脉切开术。另外,干血斑(DBS)测量有可能降低样品采集和运输的成本,同时为患者提供方便的在家采集。我们通过方法开发和分析验证对Transcend™DBSA-TLX-1-MS /MS系统进行评估,用于DBS中免疫抑制剂(他克莫司、西罗莫司和依维莫司)和抗惊厥药(左乙拉西坦和拉莫三嗪)的测量。考虑到这些免疫抑制剂相对较低的分析测量间隔(AMI),必须有足够的灵敏度,并达到所需的定量下限(LLOQ)为1 ng/mL,在LLOQ处,中间%CV小于10%。相反,抗惊厥药物相对较高的AMI需要仔细优化,以避免饱和和最小化不精确。对于所有的分析物,残留是最小的,线性和准确性使用加标样品表明充分的性能基于回归比较。因此,我们的概念验证研究表明,DBSA-TLX-1-MS /MS有潜力提供卓越的分析性能,这将有助于未来的临床验证,同时最大限度地减少执行DBS测量所需的劳动力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Automated Extraction and Quantification of Immunosuppressants  and Anticonvulsants from Dried Blood Spots: Evaluation of Transcend DBSA–TLX-1–MS/MS System

Immunosuppressants and anticonvulsant drugs are routinely quantified using liquid chromatography–tandem mass spectrometry (LC–MS/MS) in whole blood and serum, respectively, which necessitates frequent phlebotomy visits for patients. Alternatively, dried blood spots (DBS) measurements have the potential to reduce the cost of sample collection and shipping, while simultaneously enabling convenient at-home collection for patients. We evaluated Transcend™ DBSA–TLX-1–MS/MS System through method development and analytical validation for measurements of immunosuppressants (tacrolimus, sirolimus and everolimus) and anticonvulsants (levetiracetam and lamotrigine) in DBS. Given the relatively low analytical measurement interval (AMI) for these immunosuppressants, sufficient sensitivity is imperative, and the desired lower limit of quantitation (LLOQ) of 1 ng/mL was achieved, with an interday %CV less than 10% at the LLOQ. Conversely, the comparatively high AMI for the anticonvulsant drugs necessitated careful optimization to avoid saturation and minimize imprecision. For all analytes, carryover was minimal, and linearity and accuracy using spiked samples indicated adequate performance based on the regression comparisons. Therefore, our proof-of-concept study suggests that the DBSA–TLX-1–MS/MS has the potential to provide exceptional analytical performance, which will facilitate future clinical validations while minimizing labor required to perform DBS measurements.

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来源期刊
Chromatographia
Chromatographia 化学-分析化学
CiteScore
3.40
自引率
5.90%
发文量
103
审稿时长
2.2 months
期刊介绍: Separation sciences, in all their various forms such as chromatography, field-flow fractionation, and electrophoresis, provide some of the most powerful techniques in analytical chemistry and are applied within a number of important application areas, including archaeology, biotechnology, clinical, environmental, food, medical, petroleum, pharmaceutical, polymer and biopolymer research. Beyond serving analytical purposes, separation techniques are also used for preparative and process-scale applications. The scope and power of separation sciences is significantly extended by combination with spectroscopic detection methods (e.g., laser-based approaches, nuclear-magnetic resonance, Raman, chemiluminescence) and particularly, mass spectrometry, to create hyphenated techniques. In addition to exciting new developments in chromatography, such as ultra high-pressure systems, multidimensional separations, and high-temperature approaches, there have also been great advances in hybrid methods combining chromatography and electro-based separations, especially on the micro- and nanoscale. Integrated biological procedures (e.g., enzymatic, immunological, receptor-based assays) can also be part of the overall analytical process.
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