Chiral pharmacokinetics of ibuprofen enantiomers in Chinese preterm neonates with patent ductus arteriosus using a validated UHPLC-MS/ MS method

作者全名："Xiao, Dan; Jin, Ying; Zhang, Mengyu; Di, Xiangjie; Fu, Lisha; Jiang, Changke; Lai, Zhuoli; Ge, Yating; Ji, Shanmian; Zhang, Yuming; Zheng, Li; Wang, Zhenlei; Gong, Fang"

作者地址："[Xiao, Dan; Gong, Fang] Chongqing Med Univ, Yongchuan Hosp, Dept Pediat, Chongqing 402160, Peoples R China; [Xiao, Dan; Jin, Ying; Zhang, Mengyu; Di, Xiangjie; Fu, Lisha; Zheng, Li; Wang, Zhenlei] Sichuan Univ, West China Hosp, Dept Pharm, NMPA Key Lab Clin Res & Evaluat Innovat Drug, Chengdu 610041, Peoples R China; [Xiao, Dan; Jin, Ying; Zhang, Mengyu; Di, Xiangjie; Fu, Lisha; Zheng, Li; Wang, Zhenlei] Sichuan Univ, West China Hosp, Clin Trial Ctr, Chengdu 610041, Peoples R China; [Jiang, Changke] Woman & Children Hosp Yongchuan, Dept Neonates, Chongqing 402160, Peoples R China; [Lai, Zhuoli] Children Hosp Yongchuan, Dept Neonates, Chongqing 402160, Peoples R China; [Ge, Yating] Sichuan Univ, West China Sch Pharm, Dept Clin Pharm & Pharm Adm, Chengdu 610041, Peoples R China; [Ji, Shanmian] Sichuan Univ, West China Sch Pharm, Dept Pharm, Chengdu 610041, Peoples R China; [Zhang, Yuming] Sichuan Univ, West China Med Sch, Chengdu 610041, Peoples R China; [Wang, Zhenlei] Sichuan Univ, West China Hosp, Dept Pharm, NMPA Key Lab Clin Res & Evaluat Innovat Drug, 5 Telecom Rd, Chengdu 610041, Peoples R China; [Gong, Fang] Chongqing Med Univ, Yongchuan Hosp, Dept Pediat, 439 Xuanhua Rd, Chongqing 402160, Peoples R China"

通信作者："Wang, ZL (通讯作者)，Sichuan Univ, West China Hosp, Dept Pharm, NMPA Key Lab Clin Res & Evaluat Innovat Drug, 5 Telecom Rd, Chengdu 610041, Peoples R China.; Gong, F (通讯作者)，Chongqing Med Univ, Yongchuan Hosp, Dept Pediat, 439 Xuanhua Rd, Chongqing 402160, Peoples R China."

来源：JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES

ESI学科分类：CHEMISTRY

WOS号：WOS:001043511500001

JCR分区：Q2

影响因子：2.8

年份：2023

卷号：1227

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Patent ductus arteriosus; Premature neonates; (R)-ibuprofen; (S)-ibuprofen; UPLC -MS; MS; Pharmacokinetics

摘要："Persistent patent ductus arteriosus (PDA) is generally observed in preterm neonates. Oral ibuprofen is the standard treatment for closing PDA in China. To investigate the chiral pharmacokinetics of ibuprofen enantio-mers in Chinese premature infants with PDA, a simple, fast, and sensitive analytical enantioselective technology was developed with ultra-performance liquid chromatography (UPLC) - tandem mass spectrometry (MS/MS). Chromatographic separation of (R)-ibuprofen and (S)-ibuprofen was accomplished on a Lux & REG; 3 & mu;m Cellulose-3 (150 mm x 2.0 mm, 3 & mu;m) at a flow rate of 0.2 mL/min within 6 min. UPLC separation was achieved by isocratic elution with a mobile phase consisting of formic acid:water (75:1000000, v/v) and acetonitrile:methanol (1:1, v/ v). Only 50 & mu;L of plasma samples were pre-treated with acetonitrile precipitation. Ibuprofen-d3 was used as an internal standard. The standard curves of both enantiomers were linear over a concentration range of 0.0500 & mu;g/ mL to 50.00 & mu;g/mL. The method has been validated for selectivity, carryover effect, lower limit of quantification, precision, accuracy, matrix effect, extraction recovery, dilution integrity, and stability based on the existing guidelines of the National Medical Products Administration, the United States Food and Drug Administration, and the European Medicines Agency. This method has been successfully applied to investigate the pharmaco-kinetics of ibuprofen enantiomers in 9 preterm infants with PDA. Our results showed that a high chiral inversion ratio of (R)-to (S)-ibuprofen exists in Chinese preterm neonates. Further studies should be conducted to monitor drug concentration following oral administration of ibuprofen and to consider the effect of individual variations and ethnic differences in metabolizing enantiomers of ibuprofen in premature neonates with PDA."

基金机构：Youth Program of the National Natural Science Foundation of China [81903722]; Postgraduate Innovation Foundation of Yongchuan Hospital Affiliated to Chongqing Medical University [YJSCX202203]

基金资助正文：Funding. This study was supported by the Youth Program of the National Natural Science Foundation of China (81903722) and the Postgraduate Innovation Foundation of Yongchuan Hospital Affiliated to Chongqing Medical University (YJSCX202203) .