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开发并验证了一种简单可靠的 HPLC-UV 方法,用于测定吉西他滨的浓度:在药代动力学分析中的应用。

Development and Validation of a Simple and Reliable HPLC-UV Method for Determining Gemcitabine Levels: Application in Pharmacokinetic Analysis.

机构信息

Department of Pharmacology, Faculty of Medicine, University of Thessaly, 41500 Larissa, Greece.

Industrial Chemistry Laboratory, Department of Chemistry, National and Kapodistrian University of Athens, 10676 Athens, Greece.

出版信息

Medicina (Kaunas). 2024 May 25;60(6):864. doi: 10.3390/medicina60060864.

DOI:10.3390/medicina60060864
PMID:38929481
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11205493/
Abstract

: Gemcitabine has been used to treat various solid cancers, including, since 1997, metastatic pancreatic cancer. Here, we developed an HPLC-UV method to determine serum gemcitabine levels and use it in pharmacokinetic studies. : The analysis was performed after a single protein precipitation step on a reversed-phase column, isocratically eluted with sodium phosphate buffer and methanol. For the pharmacokinetic study, NOD/SCID mice received a single dose of gemcitabine at 100 mg/kg by either subcutaneous (SC) or intraperitoneal (IP) administration. Blood samples were collected at 5, 15, and 30 min and 1, 2, 4, and 6 h after the administration of gemcitabine for further analysis. : The duration of the analysis was ~12.5 min. The calibration curve was linear (r = 0.999) over the range of 1-400 μM. The mean recovery of GEM was 96.53% and the limit of detection was 0.166 μΜ. T, Tmax, Cmax, AUC, and clearance were 64.49 min, 5.00 min, 264.88 μmol/L, 9351.95 μmol/Lmin, and 0.0103(mg)/(μmol/L)/min, respectively, for the SC administration. The corresponding values for the IP administration were 59.34 min, 5.00 min, 300.73 μmol/L, 8981.35 μmol/Lmin and 0.0108(mg)/(μmol/L)/min (not statistically different from the SC administration). : A simple, valid, sensitive, and inexpensive method for the measurement of gemcitabine in serum has been developed. This method may be useful for monitoring gemcitabine levels in cancer patients as part of therapeutic drug monitoring.

摘要

: 吉西他滨已被用于治疗各种实体瘤,包括自 1997 年以来转移性胰腺癌。在这里,我们开发了一种 HPLC-UV 方法来测定血清吉西他滨水平,并将其用于药代动力学研究。: 该分析在反相柱上进行单一蛋白沉淀步骤后进行,在磷酸钠缓冲液和甲醇中等度洗脱。对于药代动力学研究,NOD/SCID 小鼠通过皮下(SC)或腹腔内(IP)给药接受 100mg/kg 的吉西他滨单次剂量。在吉西他滨给药后 5、15 和 30 分钟以及 1、2、4 和 6 小时采集血样,用于进一步分析。: 分析时间约为 12.5 分钟。校准曲线在 1-400 μM 范围内呈线性(r = 0.999)。GEM 的平均回收率为 96.53%,检测限为 0.166 μΜ。SC 给药的 T、Tmax、Cmax、AUC 和清除率分别为 64.49 分钟、5.00 分钟、264.88 μmol/L、9351.95 μmol/Lmin 和 0.0103(mg)/(μmol/L)/min,IP 给药的相应值分别为 59.34 分钟、5.00 分钟、300.73 μmol/L、8981.35 μmol/Lmin 和 0.0108(mg)/(μmol/L)/min(与 SC 给药无统计学差异)。: 已经开发出一种简单、有效、灵敏和廉价的血清中吉西他滨测定方法。该方法可用于监测癌症患者的吉西他滨水平,作为治疗药物监测的一部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3982/11205493/c41be25e7ebc/medicina-60-00864-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3982/11205493/25814080a24d/medicina-60-00864-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3982/11205493/c41be25e7ebc/medicina-60-00864-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3982/11205493/25814080a24d/medicina-60-00864-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3982/11205493/c41be25e7ebc/medicina-60-00864-g002.jpg

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The efficacy and safety of gemcitabine-based combination therapy gemcitabine alone for the treatment of advanced pancreatic cancer: a systematic review and meta-analysis.吉西他滨联合治疗与单纯吉西他滨治疗晚期胰腺癌的疗效和安全性:一项系统评价和荟萃分析。
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