A Sensitive Microscale HPLC-UV Method for the Determination of Doxofylline and its Metabolites in Plasma: An Adapted Method for Therapeutic Drug Monitoring in Children
A Sensitive Microscale HPLC-UV Method for the Determination of Doxofylline and its Metabolites in Plasma: An Adapted Method for Therapeutic Drug Monitoring in Children
复制标题
测定血浆中多索茶碱及其代谢物的灵敏微量 HPLC-UV 方法：儿童治疗药物监测的适应性方法
DOI：
10.2174/1573412914666180611103849
复制
发表时间：
2020-01-01
影响因子：
0.6
通讯作者：
Zhao，Wei
中科院分区：
文献类型：
--
作者：
Wu，Yue-E;Wu，Xiu-Fu;Zhao，Wei
Doxofylline (DXE) is a novel methylxanthine derivative used in the treatment
of asthma and Chronic Obstructive Pulmonary Diseases (COPD). Therapeutic Drug Monitoring (TDM)
has been proposed in adults, while the adapted analytical method and TDM data are still missing in
children.
A highly sensitive and stability indicating High-Performance Liquid Chromatography
(HPLC) method of DXE with caffeine as the internal standard, was developed and validated by separating
its metabolites, β-Hydroxyethyltheophylline (HPE) and Theophylline (TPE). HPLC separation is
achieved on C18 column connected to an ultraviolet detector (276 nm), using acetonitrile and ultra-pure
water in a gradient mode of elution at a flow rate of 0.9 mL/min at 25°C. A liquid-liquid extraction
method using ethyl acetate was developed with a small sample volume of plasma of 50 μL. Trough
concentration was monitored in children receiving DXE therapy.
The method was linear over the concentration ranges from 0.4-20 µg/mL for DXE, HPE and
TPE, respectively, in plasma. The limits of quantification were 0.4 µg/mL. Intra- and interday coefficients
of variation did not exceed 6.5%, and the accuracy ranged from 94.9% to 112.5%. A total of 39
children (mean age of 1.8 years, range: 0.3-5.7 years) were included. The pediatric patients had detectable
DXE concentrations with a mean value of 1.78 µg/mL (range from 0.49 to 6.36 µg/mL), and HPE
measurable concentrations with a mean value of 0.52 µg/mL (range from 0.40 to 0.82 µg/mL), while the
TPE could not be measured in any patient.
A sensitive, reliable, and adapted HPLC method has been developed for the simultaneous
analysis of DXE and its metabolites in children. The DXE and its metabolites trough concentrations
showed large inter-individual variability.
