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Simultaneous determination of lidocaine and its active metabolites in plasma by UPLC–MS/MS and application to a clinical pharmacokinetic study in liver cancer patients with laparoscopic hepatectomy
Journal of Chromatography B ( IF 3 ) Pub Date : 2022-07-09 , DOI: 10.1016/j.jchromb.2022.123362
Ying Jin 1 , Chaoqun He 2 , Xiangjie Di 1 , Lisha Fu 1 , Xiaohui Qi 1 , Runhan Liu 1 , Li Zheng 1 , Yongsheng Wang 1 , Zhenlei Wang 1 , Faping Tu 3
Affiliation  

Lidocaine, widely used as a local anesthetic, has anti-inflammatory and inhibitory effects on tumor recurrence and metastasis. To investigate the pharmacokinetics of lidocaine in liver cancer patients undergoing laparoscopic hepatectomy, a fast and sensitive analytical technique was developed. The method was adequately validated with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) to simultaneously determine the concentration of lidocaine and its metabolites in plasma. The chromatographic separation was achieved on an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) by gradient elution with a mobile phase of A (formic acid–water (1:1000, v/v)) and B (formic acid-acetonitrile (1:1000, v/v)). The accuracy and precision were verified within the concentration ranges of 10–5000 ng/mL for lidocaine, 2–1000 ng/mL for monoethylglycinexylidide (MEGX) and 2–500 ng/mL for glycinexylidide (GX). The selectivity, carry-over effect, interference between the analytes and internal standard (IS), precision and accuracy, matrix effect extraction recovery, dilution integrity and stability were satisfactory for the relevant guideline standards. The method was successfully applied to the pharmacokinetic study of lidocaine in liver cancer patients undergoing laparoscopic hepatectomy. After receiving a bolus and continuous infusion, the mean peak concentration of lidocaine was 2097 ng/mL for lidocaine, 336.6 ng/mL for MEGX and 72.66 ng/mL for GX, respectively. The mean peak time was 2.89 h for lidocaine, 5.14 h for MEGX and 9.88 h for GX, respectively. In addition, the mean half-life was 4.19 h for lidocaine and 6.92 h for MEGX. In this study, we found that the metabolism of lidocaine and MEGX might be affected by the hepatic blood flow occlusion or liver injury.



中文翻译:

UPLC-MS/MS同时测定血浆中利多卡因及其活性代谢物及其在肝癌腹腔镜肝切除术患者临床药代动力学研究中的应用

利多卡因广泛用作局部麻醉剂,具有抗炎和抑制肿瘤复发和转移的作用。为了研究利多卡因在接受腹腔镜肝切除术的肝癌患者中的药代动力学,开发了一种快速灵敏的分析技术。该方法通过超高效液相色谱-串联质谱 (UPLC-MS/MS) 充分验证,以同时测定血浆中利多卡因及其代谢物的浓度。在 Acquity UPLC BEH C 18上实现色谱分离色谱柱 (2.1 × 50 mm, 1.7 µm) 采用梯度洗脱,流动相为 A(甲酸-水 (1:1000, v/v))和 B(甲酸-乙腈 (1:1000, v/v)) )。准确度和精密度在 10–5000 ng/mL 的利多卡因、2–1000 ng/mL 的单乙基甘氨酰苯醚 (MEGX) 和 2–500 ng/mL 的甘氨酰苯醚 (GX) 浓度范围内得到验证。选择性、残留效应、分析物与内标 (IS) 之间的干扰、精密度和准确度、基质效应萃取回收率、稀释完整性和稳定性均符合相关指导标准。该方法成功应用于肝癌腹腔镜肝切除术患者利多卡因的药代动力学研究。在接受推注和连续输注后,利多卡因的平均峰值浓度为 2097 ng/mL,MEGX 和 GX 分别为 336.6 ng/mL 和 72.66 ng/mL。利多卡因的平均峰值时间为 2.89 小时,MEGX 为 5.14 小时,GX 为 9.88 小时。此外,利多卡因的平均半衰期为 4.19 小时,MEGX 为 6.92 小时。在本研究中,我们发现利多卡因和 MEGX 的代谢可能受到肝血流阻塞或肝损伤的影响。

更新日期:2022-07-12
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