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采用 LC-MS/MS 法测定干血斑中的血液右美托咪定浓度,以筛选儿科患者的治疗浓度。

Determination of blood dexmedetomidine in dried blood spots by LC-MS/MS to screen therapeutic levels in paediatric patients.

机构信息

Pharmacology Laboratory, National Institute of Paediatrics, Mexico City, Mexico.

Anaesthesiology and Critical Medicine Department, National Institute of Medical Sciences and Nutrition, Mexico City, Mexico, Intensive Care Unit, National Institute of Respiratory Diseases, Mexico City, Mexico.

出版信息

PLoS One. 2019 Jan 14;14(1):e0210391. doi: 10.1371/journal.pone.0210391. eCollection 2019.

Abstract

Dexmedetomidine is an imidazole derivative, with high affinity for α2 adrenergic receptors, used for sedation, analgesia and adjuvant anaesthesia. In this study, an analytical method for the quantification of dexmedetomidine in dried blood spots was developed, validated and applied. The drug was extracted from dried blood spot by liquid extraction; the separation was carried out by ultra high-resolution liquid chromatography in reverse phase coupled to tandem mass spectrometry method. An X Select cyano 5 μm HSS column (2.1 X 150 mm, Waters) and a mobile phase composed of 0.1% formic acid: acetonitrile [50:50 v/v], were used. The test was linear over the concentration range of 50 to 2000 pg/mL. The coefficients of variation for the intra and interday trials were less than 15%. The drug was stable under the conditions tested. The method was successfully applied for the quantification of 6 patients, aged 0 to 2 years, with classification ASA I, who underwent ambulatory surgeries, receiving a dose of 1 μg/Kg dexmedetomidine IV. The drug concentrations in the different sampling times were in the range of 76 to 868 pg/mL.

摘要

右美托咪定是一种咪唑衍生物,对 α2 肾上腺素能受体具有高亲和力,用于镇静、镇痛和辅助麻醉。在这项研究中,开发、验证和应用了一种用于测定干血斑中右美托咪定含量的分析方法。药物通过液相等效萃取从干血斑中提取;分离采用超高效液相色谱反相串联质谱法。使用 X Select Cyan 5 μm HSS 柱(2.1×150mm,Waters)和由 0.1%甲酸:乙腈[50:50 v/v]组成的流动相。检测范围为 50 至 2000pg/mL,在此范围内具有良好的线性。日内和日间精密度试验的变异系数均小于 15%。药物在测试条件下稳定。该方法成功应用于 6 名年龄 0 至 2 岁、ASA I 分级的接受 1μg/kg 右美托咪定 IV 剂量的门诊手术患者的血药浓度测定。不同时间点的药物浓度范围为 76 至 868pg/mL。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b11b/6331108/eb19a4994bb7/pone.0210391.g001.jpg

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