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Quantitative analysis method of extremely-low-concentration fluperidinol in blood plasma

A technology for quantitative analysis of haloperidol, which is applied in the direction of analysis materials, measuring devices, material separation, etc., can solve the problem of inability to evaluate drug absorption, distribution, metabolism, and excretion, and accurately quantify the blood concentration of haloperidol absorbed, Unable to guarantee the accuracy of clinical trials and other issues, to achieve good accuracy, strong anti-interference ability, and high sensitivity

Inactive Publication Date: 2021-01-01
宁波大红鹰药业股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The minimum quantification limit of the existing haloperidol tablet quantitative analysis method for biological samples is 50pg / mL. Haloperidol in very low concentration plasma samples (concentrations less than 50 pg / mL)
Therefore, the absorption, distribution, metabolism, and excretion of drugs in the body cannot be well evaluated, and the accuracy of clinical trials cannot be guaranteed.

Method used

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  • Quantitative analysis method of extremely-low-concentration fluperidinol in blood plasma
  • Quantitative analysis method of extremely-low-concentration fluperidinol in blood plasma
  • Quantitative analysis method of extremely-low-concentration fluperidinol in blood plasma

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Experimental program
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Embodiment 1

[0033] 1. Sample pretreatment

[0034] Take 50 μL of plasma sample in a 96-well plate, add 50 μL of haloperidol-d4 internal standard solution with a concentration of 200 ng / mL to the plasma sample, add 400 μL of acetonitrile solution containing 0.05-0.3% formic acid by volume, and vortex to mix After centrifugation; pipette 200 μL supernatant to a new 96-well plate, add 200 μL aqueous solution containing 0.05-0.3% formic acid by volume, seal the plate, vortex and then centrifuge, take supernatant and inject; plasma sample to be tested K 2 Plasma separated by EDTA anticoagulation was stored in a -70°C ultra-low temperature freezer;

[0035] 2. Standard curve creation

[0036] Prepare the standard working solution with the haloperidol standard product, use the standard working solution and the blank plasma added with human K2EDTA to prepare the standard curve sample, and inject the sample after the pretreatment method in step (1), with the analyte concentration as the abscissa...

Embodiment 2

[0052] With above-mentioned embodiment 1, its difference is: chromatographic condition: chromatographic column adopts C18 chromatographic column, mobile phase A and B are the mixed solution of formic acid, acetonitrile and water, and the volume ratio of acetonitrile and water in mobile phase A is 2: 98 , the amount containing formic acid is 0.1% of the total volume of the solution; the volume ratio of acetonitrile and water in mobile phase B is 98:2, and the amount containing formic acid is 0.05% of the total volume of the solution; the gradient elution procedure is as follows: 0-0.3min , the proportion of mobile phase B is 25%; 0.30-2.10min, the proportion of mobile phase B is gradually changed from 25% to 98%; 2.10-2.50min, the proportion of mobile phase B is maintained at 98%; 2.50-2.51min, the proportion of mobile phase B is 98 % gradually changed to 25%; 2.51-3.00min, the proportion of mobile phase B was maintained at 25%; the injection volume was 10μL, the flow rate was 0...

Embodiment 3

[0054] With above-mentioned embodiment 1, its difference is: chromatographic condition: chromatographic column adopts C18 chromatographic column, mobile phase A and B are the mixed solution of formic acid, acetonitrile and water, and the volume ratio of acetonitrile and water in mobile phase A is 8: 92 , the amount containing formic acid is 0.25% of the total volume of the solution; the volume ratio of acetonitrile and water in mobile phase B is 92:8, and the amount containing formic acid is 0.25% of the total volume of the solution; the gradient elution procedure is as follows: 0-0.3min , the proportion of mobile phase B is 25%; 0.30-2.10min, the proportion of mobile phase B is gradually changed from 25% to 98%; 2.10-2.50min, the proportion of mobile phase B is maintained at 98%; 2.50-2.51min, the proportion of mobile phase B is 98 % gradually changed to 25%; 2.51-3.00min, the proportion of mobile phase B was maintained at 25%; the injection volume was 2μL, the flow rate was 0...

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Abstract

The invention discloses a quantitative analysis method of extremely-low-concentration fluperidinol in blood plasma. The quantitative analysis method is characterized by comprising the following steps:1), pretreating a sample; 2), drawing a standard curve by taking the analyte concentration as an abscissa and the instrument response value as an ordinate; 3), performing liquid chromatography-tandemmass spectrometry conditions: a liquid chromatographic column adopting C18, the volume ratio of acetonitrile to water in the mobile phase A being 2: 98 to 8: 92, and the content of formic acid being0.05-0.25%, the volume ratio of acetonitrile to water in the mobile phase B being 98: 2-92: 8, and the content of formic acid is 0.05-0.25%; performinggradientelution, the mass spectrum ionization mode being an electrospray ionization positive ion mode; and 4), performing linear regression calculation: y=ax+b, y being the area ratio of the analyte to the internal standard peak, b being the intercept of the standard curve, a being the slope of the standard curve, and x being the concentration of the analyte. The method has the advantages of high accuracy and sensitivity, good specificity and strong anti-interference capability.

Description

technical field [0001] The invention relates to the technical field of drug analysis, in particular to a quantitative analysis method for extremely low concentration haloperidol in blood plasma. Background technique [0002] Haloperidol tablets are butyrophenone anti-schizophrenia drugs, which can selectively antagonize dopamine (D2) receptors and have strong anti-psychotic effects. They are used for the treatment of acute and chronic various types of schizophrenia, mania, Tourette syndrome. Haloperidol tablets are small size tablets, each containing only 2 mg of haloperidol. And when treating Tourette's syndrome, the drug dosage is 1-2 mg (0.5-1 tablet) once, 2-3 times a day. Calculated according to the average adult body weight of 60kg, the blood drug concentration in the body is extremely low after one dose of medication. In order to ensure the safety and effectiveness of medication, prevent safety problems caused by overdose and effectiveness problems caused by underd...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/06G01N30/14G01N30/72
CPCG01N30/02G01N30/06G01N30/14G01N30/72G01N2030/045
Inventor 娄晓芬宋慧慧沈幼红余剑伟
Owner 宁波大红鹰药业股份有限公司