Highly Sensitive LC–MS/MS Method for Determination of Dexamethasone in Rat Plasma and Brain Tissue: An Application to Pharmacokinetic Study in Rats

IF 1.8 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Rama Murthi Bestha, Ashok Zakkula, Madipelli Keerthana, Sandeep Kaddare, Niranjan Veerla, Ramesh Mullangi, Sreekanth Dittakavi
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Abstract

A highly sensitive and rapid LC–MS/MS method was developed and validated for the quantification of dexamethasone in rat plasma and brain tissue. Protein precipitation method was used for sample preparation. The separation of dexamethasone and the IS (labetalol) was achieved on an Atlantis dC18 column using an isocratic mobile phase (10 mM ammonium formate and acetonitrile, 25/75, v/v) delivered at 0.7 mL/min flow-rate. Dexamethasone and the IS were eluted at 1.03 and 1.06 min, respectively. The MS/MS transitions monitored were m/z 393.100 → 373.100 (dexamethasone) and 329.100 → 91.100 (IS). Method validation was performed as per FDA guidelines and all parameters met the acceptance criteria. The assay was validated with a quantification range of 0.05–1046 ng/mL in both matrices. The intraday and interday precision for were in the range of 2.62–7.28 and 2.76%–6.98% and 2.24–6.85 and 2.97%–6.37%, in plasma and brain tissue, respectively. Dexamethasone was stable in a series of stability conditions in both matrices. Post-intravenous administration to rats, dexamethasone concentrations in plasma and brain tissue were quantifiable up to 24 and 10 h, respectively. Dexamethasone half-life was ~2.30 h. Dexamethasone exhibited low clearance and moderate volume of distribution in plasma but in brain tissue the clearance and volume of distribution were high.

高灵敏度LC-MS/MS法测定大鼠血浆和脑组织中地塞米松的药代动力学研究
建立了一种高灵敏、快速的大鼠血浆和脑组织中地塞米松的LC-MS/MS定量方法。样品制备采用蛋白质沉淀法。地塞米松和拉贝他洛尔在Atlantis dC18色谱柱上分离,采用等密度流动相(10 mM甲酸铵和乙腈,25/75,v/v),流速为0.7 mL/min。地塞米松和IS分别在1.03和1.06 min洗脱。监测的MS/MS转变为m/z 393.100→373.100(地塞米松)和329.100→91.100 (IS)。方法验证按照FDA指南进行,所有参数均符合验收标准。两种基质的定量范围为0.05-1046 ng/mL。血浆和脑组织的日内、日间精密度分别为2.62 ~ 7.28和2.76% ~ 6.98%,2.24 ~ 6.85和2.97% ~ 6.37%。地塞米松在两种基质的一系列稳定条件下都是稳定的。大鼠静脉给药后,分别在24小时和10小时内测量血浆和脑组织中的地塞米松浓度。地塞米松半衰期~2.30 h。地塞米松在血浆中清除率低,分布体积适中,但在脑组织中清除率高,分布体积大。
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来源期刊
Biomedical Chromatography
Biomedical Chromatography 生物-分析化学
CiteScore
3.60
自引率
5.60%
发文量
268
审稿时长
2.3 months
期刊介绍: Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.
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