Method for determining concentration of nilotinib in blood plasma

A nilotinib and blood plasma technology, which is applied in the field of determination of nilotinib concentration in plasma, can solve the problems that the measured substance and the internal standard cannot change synchronously, affect the repeatability and measurement accuracy of the method, and achieve a simple pretreatment method , easy operation and high sensitivity

Pending Publication Date: 2020-08-11
THE SECOND HOSPITAL AFFILIATED TO SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Non-isotopic internal standards may have matrix effects, and the measured substance and internal sta...

Method used

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  • Method for determining concentration of nilotinib in blood plasma
  • Method for determining concentration of nilotinib in blood plasma
  • Method for determining concentration of nilotinib in blood plasma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Embodiment 1: the mensuration of nilotinib concentration in human plasma;

[0028] 1. Experimental materials and instruments

[0029] Nilotinib reference substance: provided by Suzhou Terui Pharmaceutical Co., Ltd., batch number: b18018;

[0030] [ 13 C, 2 h 3 ]-Nilotinib reference substance: provided by Alsachim, batch number: DH-ALS-16-007-P1; Test water: ultrapure water; Methanol, formic acid: chromatographically pure (Merck Company); Ammonium acetate: analytically pure (Sinopharm Chemical Reagents Ltd.).

[0031] API4000 LC / MS / MS coupled instrument (AB Scisex, USA), chromatographic workstation:

[0032] Analyst 1.6; Mettler XS 105DU electronic balance (Mettler, Switzerland); Eppendorf Centrifuge 5424R high-speed low-temperature centrifuge (Eppendorf, Germany); KDC-2046 low-speed refrigerated centrifuge (Anhui Zhongke Zhongjia Scientific Instrument Co., Ltd.); Millipore Drict-Q5 ultrapure water machine (French Millipore Company).

[0033] 2. Liquid conditions ...

Embodiment 2

[0058] Embodiment 2: the mensuration of nilotinib concentration in the plasma of female subjects;

[0059] Referring to Example 1, a healthy female subject took 200 mg of Nilotinib Capsules on an empty stomach, and took it with 240 mL of warm boiled water; 3 mL of peripheral venous blood was collected 3 hours after administration, injected into a heparin tube, centrifuged (4000 r min -1 , 5min), draw 200 μL of the subject’s plasma sample, and accurately add an internal standard of 500 ng·mL -1 [ 13 C, 2 h 3 ]-50 μL of Nilotinib solution, vortexed for 10 s, added 610 μL of methanol to precipitate protein, vortexed for 1 min, and centrifuged at 15000 rpm, 4°C for 10 min. Draw 100 μL of the supernatant into the injection bottle, add 700 μL of deionized water, and draw 20 μL of the mixed solution for injection. The results showed that 3 hours after oral administration of 200 mg nilotinib capsules on an empty stomach, the nilotinib content in the plasma of a healthy female subj...

Embodiment 3

[0060] Embodiment 3: the mensuration of nilotinib concentration in the blood plasma of experimenter 72h after administration;

[0061] Referring to Example 1, 5 healthy male subjects and 1 female subject took 200 mg of nilotinib capsules on an empty stomach, and took them with 240 mL of warm water; 72 hours after administration, 3 mL of peripheral venous blood was collected and injected into a heparin tube. Centrifugal (4000r·min -1 , 5min), draw 200 μL of subject’s plasma sample, and accurately add internal standard 500ng·mL -1 [ 13 C, 2 h 3 ]-Nilotinib solution 50 μL, vortex 10s, add 610 μL methanol to precipitate protein, vortex 1min, centrifuge at 15000rpm, 4℃ for 10min. Draw 100 μL of the supernatant into the injection bottle, add 700 μL of deionized water, draw 20 μL of the mixed solution for injection. The results showed that 72 hours after oral administration of Nilotinib Capsules 200 mg on an empty stomach, the contents of Nilotinib in the plasma of 5 healthy mal...

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Abstract

The invention provides a method for determining the concentration of nilotinib in blood plasma. The method comprises the following steps: pretreating a blood plasma sample, and carrying out liquid chromatography separation, mass spectrometry determination, calculation and the like on the pretreated blood plasma sample. Compared with the prior art, the method has the following advantages: (1) the pretreatment method is simple and convenient; (2) the specificity is high; (3) the sensitivity is high: the lowest quantification limit of plasma is 2.5 ng.mL<-1>; (4) isotope internal standard: no matrix effect exists; and (5) the method is rapid, simple, convenient and accurate to operate, high in sensitivity and low in detection limit. A basis is provided for clinical blood drug concentration determination of nilotinib, and the method serves research, development and clinical application of new drugs. According to the method, the linear range of a plasma standard curve is 2.5-2000 ng.mL<-1>,and the within-run precision RSD and between-run precision RSD are both smaller than 15%.

Description

technical field [0001] The invention relates to a method for measuring the concentration of nilotinib in blood plasma. Background technique [0002] Nilotinib is an oral inhibitor of tyrosine kinases targeting BCR-Abl, c-Kit, PDGFR, DDR, and related receptors. Clinically, it is mainly used for the treatment of chronic myeloid leukemia (CML). [0003] The study of drug pharmacokinetics and bioequivalence is evaluated by measuring the pharmacokinetic parameters of drugs, and the detection and analysis of drugs is very important. Nilotinib biological samples have complex components, large matrix interference, difficult to obtain samples and small quantities, and the concentration of analytes is usually very low. Therefore, the requirements for the separation and analysis technology of biological samples are getting higher and higher, and it is urgent to establish A highly sensitive and selective method for nilotinib plasma concentration analysis. LC-MS / MS method is the prefe...

Claims

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Application Information

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IPC IPC(8): G01N30/02G01N30/72
CPCG01N30/02G01N30/72G01N2030/045
Inventor 黄明张全英王蒙宗顺麟
Owner THE SECOND HOSPITAL AFFILIATED TO SUZHOU UNIV
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