Optimizing cancer patient care with a robust assay for 5-fluorouracil quantification and in-vitro stability in human blood for therapeutic drug monitoring

IF 1.7 Q3 MEDICAL LABORATORY TECHNOLOGY Practical Laboratory Medicine Pub Date : 2024-05-01 DOI:10.1016/j.plabm.2024.e00415
Murari Gurjar , K. Ambedkar Priyan , Priyanka Asia , Uday Kumar , Kajal Shukla , Bal Krishna Mishra , Akhil Kapoor , Pratibha Gavel
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Abstract

Background

The plasma concentration of 5-Fluorouracil (5-FU) is affected by numerous factors, thereby limiting its efficacy. The current therapeutic regimen's doses based on body surface area (BSA) are linked to increased toxicity and sometimes inadequate drug exposure.

Aim and objectives

The study aims to develop an in-vitro assay to monitor 5-Fluorouracil's therapeutic efficacy in cancer patients' blood samples, focusing on pharmacokinetics to improve therapy precision.

Materials and methods

Drug levels were determined from standards, quality controls, and experimental samples using protein precipitation, liquid-liquid extraction, and separation using a C18 analytical column with an isocratic program.

Result

In EXP-1A, the mean concentration of 5-Fluorouracil was 1.15 μg/ml; in EXP-1B, it was 1.16 μg/ml, while in EXP-1C, the mean concentration was 0.9 μg/ml. The percentage difference in mean 5-Fluorouracil concentration between the experiment sample containing a DPD inactivator and EXP-1C (without a DPD inactivator) was 21.5 % higher for EXP-1A and 0.68 % higher for EXP-1B. In the second phase of the experiment, the overall stability of 5-Fluorouracil in samples containing a DPD inactivator was 24.5 % superior compared to samples without a DPD inactivator.

Conclusion

A modified extraction technique has been developed to accurately measure 5-Flourouracil concentration in blood, preserving its stability and concentration by adding a DPD inactivator.

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利用用于治疗药物监测的 5-氟尿嘧啶在人体血液中定量和体外稳定性的可靠测定,优化癌症患者护理
背景5-氟尿嘧啶(5-FU)的血浆浓度受多种因素影响,从而限制了其疗效。目的和目标本研究旨在开发一种体外检测方法,用于监测癌症患者血液样本中 5-氟尿嘧啶的疗效,重点关注药代动力学,以提高治疗的精确性。结果在 EXP-1A 中,5-氟尿嘧啶的平均浓度为 1.15 μg/ml;在 EXP-1B 中,5-氟尿嘧啶的平均浓度为 1.16 μg/ml;在 EXP-1C 中,5-氟尿嘧啶的平均浓度为 0.9 μg/ml。含有 DPD 灭活剂的实验样品与 EXP-1C(不含 DPD 灭活剂)之间的 5-氟尿嘧啶平均浓度的百分比差异为:EXP-1A 高 21.5%,EXP-1B 高 0.68%。在实验的第二阶段,与不含 DPD 灭活剂的样本相比,含 DPD 灭活剂的样本中 5-氟尿嘧啶的总体稳定性高出 24.5%。
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来源期刊
Practical Laboratory Medicine
Practical Laboratory Medicine Health Professions-Radiological and Ultrasound Technology
CiteScore
3.50
自引率
0.00%
发文量
40
审稿时长
7 weeks
期刊介绍: Practical Laboratory Medicine is a high-quality, peer-reviewed, international open-access journal publishing original research, new methods and critical evaluations, case reports and short papers in the fields of clinical chemistry and laboratory medicine. The objective of the journal is to provide practical information of immediate relevance to workers in clinical laboratories. The primary scope of the journal covers clinical chemistry, hematology, molecular biology and genetics relevant to laboratory medicine, microbiology, immunology, therapeutic drug monitoring and toxicology, laboratory management and informatics. We welcome papers which describe critical evaluations of biomarkers and their role in the diagnosis and treatment of clinically significant disease, validation of commercial and in-house IVD methods, method comparisons, interference reports, the development of new reagents and reference materials, reference range studies and regulatory compliance reports. Manuscripts describing the development of new methods applicable to laboratory medicine (including point-of-care testing) are particularly encouraged, even if preliminary or small scale.
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