生物分析方法的开发和验证,以确定olutasidenib及其在药物动力学研究中的应用
Madhusudhana Reddy Nimmakayala1, Kuruva Rangamuni1, Jasti Surendra2
1Department of Chemistry, Koneru Lakshmaiah Education Foundation Green Fields, Vaddeswaram Guntur Andhra Pradesh 522302 India atluri.deepti1984@gmail.com +91 9490494699.
RSC advances
|July 9, 2025
概括
一种新的LC-MS/MS方法准确地测量了老鼠血中的olutasidenib,用于药理动力学研究. 这种经过验证的方法支持使用olutasidenib (IDH1抑制剂) 治疗急性髓性白血病 (AML).
科学领域:
- 药理学和毒理学 药理学和毒理学
- 分析化学 分析化学
- 在瘤学瘤学.
背景情况:
- 奥卢塔西迪尼布是一种FDA批准的抑制剂,向异酸脱酶-1 (IDH1) 突变.
- 它是复发性或耐药性急性髓性白血病 (AML) 的有效疗法,具有易感的IDH1突变.
- 经过广泛的审查过程,FDA批准于2022年12月获得.
研究的目的:
- 开发和验证一种灵敏而准确的液体染色学-并联质谱法 (LC-MS/MS) 方法.
- 为了确定老鼠血中olutasidenib的度.
- 为了支持olutasidenib的药理学研究.
主要方法:
- 液体染色学-双重质谱法 (LC-MS/MS) 用于分析.
- 易布鲁替尼被用作内部标准进行比较.
- 液体-液体提取 (LLE) 用于样品的准备.
- 为了分离,使用了一个特定的Inertsil ODS柱和一个由Acetonitrile (ACN) 和酸盐缓冲剂 (AmF) 组成的移动相.
主要成果:
- LC-MS/MS方法在3.0-60.0 ng/mL的度范围内显示出高精度,相关系数 (r2) ≥0.999.
- 试验内部精度显示变化系数 (CV) 在0.31%至3.41%之间.
- 在不同的质量控制水平上,准确度从97.40%到99.69%不等.
结论:
- 开发的LC-MS/MS方法是准确,精确和有效的,用于量化老鼠血中的olutasidenib.
- 这种经过验证的方法适用于olutasidenib的药理学研究.
- 这些发现有助于理解olutasidenib在体内表现的行为,有助于其在AML中的治疗应用.
更多相关视频
相关概念视频
Protein-Drug Binding: Determination Methods
316
Determining protein-drug binding can be achieved through indirect and direct methods, each providing valuable insights into the interaction between proteins and drugs.
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
316
Analysis of Population Pharmacokinetic Data
394
Analysis of population pharmacokinetic data involves studying the behavior of drugs within diverse populations to understand their pharmacokinetic parameters. Traditional pharmacokinetic methods typically involve collecting samples from a few individuals and estimating these parameters. While these methods are commonly used, they have limitations in capturing the variability in drug response among individuals or heterogeneous populations. Population pharmacokinetics is employed to address these...
394
Methods for Studying Drug Absorption: In situ
365
In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
365
Analysis Methods of Pharmacokinetic Data: Model and Model-Independent Approaches
233
Drug disposition in the body is a complex process and can be studied using two major approaches: the model and the model-independent approaches.
The model approach uses mathematical models to describe changes in drug concentration over time. Pharmacokinetic models help characterize drug behavior in patients, predict drug concentration in the body fluids, calculate optimum dosage regimens, and evaluate the risk of toxicity. However, ensuring that the model fits the experimental data accurately...
The model approach uses mathematical models to describe changes in drug concentration over time. Pharmacokinetic models help characterize drug behavior in patients, predict drug concentration in the body fluids, calculate optimum dosage regimens, and evaluate the risk of toxicity. However, ensuring that the model fits the experimental data accurately...
233
One-Compartment Open Model: Wagner-Nelson and Loo Riegelman Method for ka Estimation
726
This lesson introduces two critical methods in pharmacokinetics, the Wagner-Nelson and Loo-Riegelman methods, used for estimating the absorption rate constant (ka) for drugs administered via non-intravenous routes. The Wagner-Nelson method relates ka to the plasma concentration derived from the slope of a semilog percent unabsorbed time plot. However, it is limited to drugs with one-compartment kinetics and can be impacted by factors like gastrointestinal motility or enzymatic degradation.
On...
On...
726
Preclinical Development: Overview
4.9K
Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...
4.9K


