Method and kit for detecting five psychotropic drugs and main metabolites thereof in blood

Abstract

The invention belongs to the field of drug detection, and particularly relates to a method and a kit for detecting five psychotropic drugs and main metabolites thereof in blood. The five psychotropicdrugs and the main metabolites thereof comprise: olanzapine and demethyl olanzapine, risperidone and 9-hydroxy risperidone, aripiprazole and dehydrogenated aripiprazole, Escitalopram and demethyl citalopram, sertraline and N-demethyl sertraline. Accoridng to the method provided by the invention, a pair of quantitative ion pairs is respectively selected for each detection substance, a relative retention time thereof is used as a qualitative basis, and a standard curve is made by using a standard product for quantification; furthermore, the accuracy and effectiveness of the method are evaluatedfrom quality control of three low, middle and high levels, thereby avoiding distortion of the detection result; and meanwhile, an internal standard working solution is applied to correction, so that matrix effects can be avoided, and accurate quantification is realized. The method provided by the invention has the advantages of simple and rapid operation, high flux and low cost, and can be appliedto the therapeutic drug monitoring of the psychotropic drugs in the clinical work of the psychiatry department.

Description

technical field [0001] The invention belongs to the field of drug detection, and in particular relates to a method and a kit for detecting five psychotropic drugs and their main metabolites in blood. Background technique [0002] Most of the mental illnesses are chronic diseases. At present, the treatment of mental illness is still dominated by drug therapy, and most patients need long-term or even life-long medication. How to choose and use psychotropic drugs well to achieve the best curative effect and the least adverse reactions is an important problem faced by drug treatment of mental illness. Therefore, therapeutic drug monitoring of psychotropic drugs is an important means to adjust the dosage, optimize the treatment plan, and achieve precise treatment. The present invention provides a method and kit for accurate, convenient and rapid determination of olanzapine, risperidone, aripiprazole, escitalopram, sertraline and their main metabolites in blood samples, and the ...

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.

Another example is a Chinese patent application (application number: 201810878811.X, publication number: CN109085264A) which discloses a "kit for detecting antidepressants in serum and plasma by liquid chromatography tandem mass spectrometry and its application", and can simultaneously detect 12 It is an antidepressant drug, but it also has some defects, including: 1) simultaneous detection of 12 drugs caused unnecessary waste, 2) only venlafaxine and fluoxetine were tested for the original drug and metabolites at the same time, which could not be accurately evaluated The overall effect of the drug, 3) The linear ranges of the two substances and the two metabolites are consistent, which does not conform to the actual clinical situation. Because the reference ranges of clinical samples are different, the reference ranges of different drugs need to be adjusted according to the actual situation

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.

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