A validated method for the determination of doxofylline and its pharmacokinetic application in healthy volunteers.

IF 1.8 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS

Bioanalysis Pub Date : 2025-07-01 Epub Date: 2025-07-30 DOI:10.1080/17576180.2025.2535950

Yonghua Yu, Danrui Liu, Hangyu Zhao, Menglong Dai, Yu Hu, Kaiwei Luo, Huina Zhang

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引用次数: 0

Abstract

Background: Current HPLC-based methods for doxofylline analysis lack speed and precision. A rapid, specific, and sensitive UPLC-MS/MS method was developed for the determination of doxofylline in this study.

Research design and methods: This method was fully validated and doxophylline-d4 was used as an internal standard. A Kinetex-C18 column (EVO 100Å, 50 × 2.1 mm, 5 μm) was used for the separation procedure, with mobile phases consisting of 0.3% formic acid (A) and 90% acetonitrile solution with 0.3% formic acid (B). The total runtime of the gradient elution procedure was 2.6 minutes. The mass spectrometry analysis was carried out employing a multiple reaction monitoring model and using the transitions of m/z 267.000→181.000 for doxofylline and m/z 271.200→181.100 for the internal standard.

Results: The linear range of detection for doxophylline was between 20.0 to 16,000 ng/mL. The intra-batch accuracy deviations of each concentration level ranged from -8.0% to 2.5%, while the intra-batch precisions ranged from 1.3% to 9.0%. And the inter-batch accuracy deviations were -5.8% ~0.8%, while the inter-batch precisions were 2.2% ~7.0%.

Conclusions: This method was applied to pharmacokinetic clinical trials of single oral administration of doxophylline tablets successfully.

Clinical trial registration: www.clinicaltrials.gov identifier is CTR20240006 and CTR20233665.

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一种有效的多索茶碱测定方法及其在健康志愿者体内的药动学应用。

背景：目前基于高效液相色谱的多索茶碱分析方法缺乏速度和精度。建立了一种快速、特异、灵敏的超高效液相色谱-串联质谱法测定多索茶碱的方法。研究设计与方法：以doxophylline-d4为内标，对该方法进行了充分验证。采用Kinetex-C18色谱柱（EVO 100Å， 50 × 2.1 mm, 5 μm）进行分离，流动相为0.3%甲酸(A)和含有0.3%甲酸(B)的90%乙腈溶液。梯度洗脱过程的总运行时间为2.6分钟。质谱分析采用多反应监测模型，多索茶碱采用m/z 267.000→181.000过渡段，内标采用m/z 271.200→181.100过渡段。结果：茶碱的检测线性范围为20.0 ~ 16000 ng/mL。各浓度水平的批内准确度偏差范围为-8.0% ~ 2.5%，批内准确度偏差范围为1.3% ~ 9.0%。批间准确度偏差为-5.8% ~0.8%，批间准确度偏差为2.2% ~7.0%。结论：该方法可用于多茶碱片单次口服的药动学临床试验。临床试验注册：www.clinicaltrials.gov标识符为CTR20240006和CTR20233665。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioanalysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

3.30

自引率

16.70%

发文量

审稿时长

2 months

期刊介绍： Reliable data obtained from selective, sensitive and reproducible analysis of xenobiotics and biotics in biological samples is a fundamental and crucial part of every successful drug development program. The same principles can also apply to many other areas of research such as forensic science, toxicology and sports doping testing. The bioanalytical field incorporates sophisticated techniques linking sample preparation and advanced separations with MS and NMR detection systems, automation and robotics. Standards set by regulatory bodies regarding method development and validation increasingly define the boundaries between speed and quality. Bioanalysis is a progressive discipline for which the future holds many exciting opportunities to further reduce sample volumes, analysis cost and environmental impact, as well as to improve sensitivity, specificity, accuracy, efficiency, assay throughput, data quality, data handling and processing. The journal Bioanalysis focuses on the techniques and methods used for the detection or quantitative study of analytes in human or animal biological samples. Bioanalysis encourages the submission of articles describing forward-looking applications, including biosensors, microfluidics, miniaturized analytical devices, and new hyphenated and multi-dimensional techniques. Bioanalysis delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for the modern bioanalyst.