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Method and kit for detecting five psychoactive drugs and main metabolites in blood

A technology for psychotropic drugs and metabolites, applied in the direction of measuring devices, instruments, scientific instruments, etc., can solve the problems of difficult chromatographic separation of various targets, unsuitable linear range, single type of detection drugs, etc., to achieve stable clinical test results, The linear range is set reasonably to avoid the effect of distortion of the detection results

Active Publication Date: 2021-07-13
BEIJING HUILONGGUAN HOSPITAL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantages of this method include: 1) the 35 drugs are not all commonly used drugs in clinical practice, and patients with mental illness are generally treated with one drug or a combination of two drugs, and the simultaneous detection of 35 drugs causes unnecessary waste. The external standard method is used for the detection of drugs. The external standard method cannot eliminate the matrix effect in the detection process, which is not conducive to accurate quantification. Most of the current published literature and patents have replaced the external standard method with the internal standard method.
Chinese patent (patent number: 201610730994.1, publication number CN106168610B) discloses a kind of: "The method for determining the concentration of clozapine in plasma by high performance liquid chromatography mass spectrometry", which provides a method using high performance liquid chromatography tandem mass spectrometry, and The method of using risperidone as an internal standard to detect clozapine psychotropic drugs, but this method is a method for specific psychotropic drugs-clozapine drugs, is not suitable for the simultaneous measurement of multiple psychotropic drugs, and it utilizes risperidone Ketone is used as an internal standard, not an isotope as an internal standard, which cannot completely eliminate the matrix effect, which is not conducive to accurate quantification
[0005] First, there is a matrix effect. Some methods still use the external standard method for drug concentration detection. There is a matrix effect and cannot be accurately quantified. At present, most LC-MS / MS methods use isotopes instead of other internal standards to correct matrix effects, etc. impact, the external standard method has been phased out
[0006] Second, the types of drugs to be tested are not suitable for clinical use, and the types of drugs to be tested are single or too many. Since patients with mental illness generally use one drug or two drugs in combination, the type of drugs to be tested is single and the throughput is low, which is not conducive to carrying out more tests. Project; There are too many types of testing drugs, resulting in high costs and waste of resources, and it is not easy to perform large-scale clinical testing. Therefore, it is necessary to develop a reasonable method based on clinical needs.
[0007] Third, the linear range is not suitable. The linear range of many drugs in the measurement method of the prior art is unreasonable, has not been verified by clinical samples, and is not suitable for clinical testing
[0008] Fourth, the sensitivity is low. In the process of detecting multiple drugs at the same time, there are problems such as the difficulty of complete chromatographic separation and co-elution of multiple targets, resulting in relatively low sensitivity and affecting the accuracy of detection.

Method used

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  • Method and kit for detecting five psychoactive drugs and main metabolites in blood
  • Method and kit for detecting five psychoactive drugs and main metabolites in blood
  • Method and kit for detecting five psychoactive drugs and main metabolites in blood

Examples

Experimental program
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Effect test

preparation example Construction

[0073] 1. Preparation of samples in the sample to be tested, as described by step.

[0074] 2. Preparation of Standard Immoving Sample: A variety of drugs, mixed standard working fluids after dilution of negative plasma or serum, add 2-4 times, preferably 3 times volume internal standard working fluid, mix, Centrifuge, prepare it.

[0075] 3, preparation of mass control materials: various drugs, various drugs, and various gradients, etc., add 2-4 times, preferably 3 times volume internal standard working fluid, mixing , Centrifugally take the supernatant, ready to sample.

[0076] Step three, high performance liquid chromatography - tandem mass spectrometry (HPLC-MS / MS) test:

[0077] Preferably, the same volume of the above-described sample liquid, mixed standard inlet liquid, and quality control material injection liquid in sample detection.

[0078] The instrument adopted in this step is: SCIEX 4500md triple four-stage rod mass spectrometer (US, Sciex Company), Shimadzu High ...

Embodiment 1

[0104] This example is a method of detecting five psychotropic drugs in the blood and its main metabolites, including the following steps:

[0105] 1, blood sample pretreatment:

[0106] Precision to 3 μl of plasma or serum samples in 1.5 ml EP tube, then add 300 μl of the internal standard working fluid (formulation method to see below 3), vortex mixing 1 min. 10 min at 4 ° C, 14000 rpm was centrifuged, and 100-200 μL of the supernatant was used to obtain a sample (i.e., sample liquid to be tested).

[0107] 2, mixed standard working fluid:

[0108] (1) Accurately weigh the amount of quine, N-denyl quinopalate, chlorosa, N-dethylchlorosa, Wen Laffaxin, O-demethyl Lafa, Lavoxetine, rice nitrogen, with methanol, respectively, a standard reserve solution for a mass concentration of 1 mg / mL, respectively.

[0109] (2) Accurately move the appropriate amount of standard stock solution, separately formulated a standard intermediate working fluid with 50 vol% methanol, in the intermedia...

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Abstract

The invention belongs to the field of drug detection, and in particular relates to a method and a kit for detecting five kinds of psychotropic drugs and main metabolites in blood. The five psychotropic drugs and their main metabolites are: quetiapine, N-dealkylated quetiapine, clozapine, N-desmethylclozapine, venlafaxine, O-desmethylated Lafaxine, duloxetine, mirtazapine. For each detection substance, the present invention selects a pair of quantitative ion pairs respectively, uses its corresponding retention time as a qualitative basis, makes a standard curve quantitatively with standard products; and uses three levels of quality control products to investigate the accuracy of the method. To avoid distortion of the test results; at the same time, the internal standard working solution is used for calibration, which can avoid matrix effects and achieve accurate quantification. The invention has the advantages of simple and quick operation, high throughput and low cost, and can be applied to the clinical work of psychiatry to monitor psychotropic drugs for therapeutic drugs.

Description

Technical field [0001] The present invention belongs to the field of drug detection, and specifically, the present invention specifically involves detecting 5 psychotropic drugs and the primary metabolites in the blood. Background technique [0002] Multi-chronic diseases, the current treatment of mental illness is still mainly drug therapy, most patients need long-term or even lifetime. How to choose, good psychotropic drugs, the best way to achieve the effect, the least adverse reactions is an important issue facing mental illness medication. Therefore, the treatment of drug monitoring for psychotropic drugs is an important means of adjusting the dose, optimized treatment plan, and achieving precision treatment. The present invention provides a method and kit that can accurately, conveniently, rapidly measuring blood samples, chlorose, chlorosa, serraphylation, rocketine, rice nitrogen, and its main metabolites, and these five Drugs are currently more widely used in clinical ap...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N30/88G01N30/06G01N30/14
CPCG01N30/06G01N30/14G01N30/88G01N2030/045
Inventor 杨甫德安会梅谭云龙栗琳陆开智王黎辉谭淑平陈松姚尚武齐思远梁伟业白璐源马泊涛王永前武红梅刘枫蔡博伦王冬倪伟丁建军李彩霞
Owner BEIJING HUILONGGUAN HOSPITAL
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