CN115290775A - Quality control product of mental drugs, kit, preparation method and application thereof - Google Patents
Quality control product of mental drugs, kit, preparation method and application thereof Download PDFInfo
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Abstract
The invention provides a quality control product, a kit and application thereof, wherein the quality control product comprises quality control psychotropic drugs, a stabilizer and a matrix, and the quality control product is prepared into freeze-dried powder after being mixed; the quality control psychotropic drugs comprise duloxetine, haloperidol, ziprasidone, olanzapine, clozapine, N-norclozapine, quetiapine, risperidone and paliperidone; the stabilizer is 2,6-di-tert-butyl-4-methylphenol. The quality control product is used for mass spectrum inspection and biochemical experiments of the concentration of the psychotropic drugs, has the technical effects of good stability, repeated freeze thawing, easy transportation and storage and simple and convenient preparation method.
Description
Technical Field
The invention relates to an in-vitro detection reagent, and in particular relates to a quality control product of a mental medicament, a kit, a preparation method and application thereof.
Background
The traditional antipsychotic has low effective concentration, narrow treatment window, complex drug action mechanism and obvious adverse reaction, and the adverse reaction of the drug is closely related to the dose of the drug. Mental diseases are easy to relapse, the treatment time is long, long-term and even lifelong medication is needed, and the risk of drug combination is accompanied. For these drugs, drug concentration detection is of great importance. The accurate and precise detection of the drug concentration cannot be separated from the daily quality management, and the use of uniform and stable quality control products is one of the indispensable means for the quality management. The quality control product is used for detecting and controlling the precision of clinical detection projects in a laboratory, evaluating the deviation between different detection systems through the indoor quality control and indoor change, further searching problems and improving quality, and finally ensuring the comparability of detection results between different laboratories, so that the quality of the quality control product is the basis and key link of laboratory quality management. There are many kinds of antipsychotic drugs, and some of them are not stable chemically or biologically. [ development of suitable and long-term stable quality control substances for clinical testing as ziprasidone reported in the literature Formulation and Stabilization of dual Hydrochloride Delayed Release Pellets with the air Non Ionic Barrier Layer ] is a quality key to ensure accurate detection of antipsychotic drug concentrations. In addition, the quality control product is required to have the characteristics of accuracy, no interference, easy storage and transportation and the like.
The LC-MS technology is an important research means in drug identification and analysis due to the combination of high separation efficiency of chromatography and high sensitivity of mass spectrum. With the gradual clinical progress of the LC-MS method, the advantages of the LC-MS method in the TDM multi-drug combination analysis are prominent, the simultaneous analysis of a plurality of compounds can be realized in a short time, the LC-MS method is particularly suitable for the trace analysis of low-concentration psychotropic drugs, and the LC-MS method gradually becomes the mainstream technology and the gold standard of the clinical drug concentration analysis. The clinical quality control product suitable for the LC-MS technology is available, and the LC-MS drug concentration detection is more favorably changed into the standard technology of clinical examination.
In recent years, mass spectrum commercial kits for simultaneously detecting various psychotropic drugs are rarely available, and quality control products for mass spectrum detection are few and few, and the products do not take the key performance of optimizing stability, applicability and the like as a research and development key point, so that accurate, effective and convenient quality control products are still lacking clinically. The drug concentration items detected by mass spectrometry mostly have no safe and qualified commercial quality control products, and the quality control products used by the existing drug concentration detection items also have the defects of short validity period, poor stability and the like, and the factors greatly increase the quality control difficulty of the drug concentration mass spectrometry.
Therefore, the invention of a stable human plasma quality control product containing various medicaments is urgently needed in the field, so as to relieve the urgent need of a clinical mass spectrometry laboratory.
Disclosure of Invention
The invention aims to provide a quality control product which has stable performance and long validity period and is beneficial to the performance of mass spectrometric inspection of drug concentration.
The invention aims to provide a quality control product kit containing 9 psychotropic drugs, and the preparation process comprises the following steps:
(1) Taking 9 high-concentration stock solutions containing psychotropic analytes, and diluting the stock solutions by using an organic solvent containing a stabilizer to obtain a high-concentration analyte working solution to be added;
(2) Adding a stabilizing agent and a high-concentration analyte working solution in a certain proportion into the selected matrix, and fully and uniformly mixing to prepare low-concentration and high-concentration serum/plasma quality control substance solutions containing 9 psychotropic drugs;
(3) Accurately sucking 1mL of serum/plasma quality control substance solution, subpackaging the solution in 3mL of glass bottles, performing vacuum freeze-drying to prepare a quality control substance freeze-drying agent, and packaging 1-2 bottles of low-concentration and high-concentration quality control substance freeze-drying agents into a kit for clinical detection;
(4) When the product is used, the bottle cap of a quality control product is carefully opened at room temperature (15-25 ℃) in an environment without air circulation or direct sunlight, 1mL of deionized water or distilled water is accurately added, the bottle cap is covered, standing is carried out until the product is completely dissolved (about 20 minutes), then the product is slightly reversed and rotated to be uniformly mixed, and after the product is fully mixed, sampling and measuring are carried out. If the quality control product needs to be repeatedly frozen and thawed for use after redissolving, the bottle cap is immediately covered and put back into a refrigerator for storage after sampling is finished each time, and the bottle cap is placed at room temperature for fully thawing and is uniformly mixed before next use for sampling and detecting.
The first aspect of the invention provides a quality control product, which comprises quality control psychotropic drugs, a stabilizer and a matrix, wherein the drugs, the stabilizer and the matrix are mixed and then prepared into freeze-dried powder; the quality control mental medicament comprises duloxetine, haloperidol, ziprasidone, olanzapine, clozapine, N-norclozapine, quetiapine, risperidone and paliperidone; the stabilizer is 2,6-di-tert-butyl-4-methylphenol.
The mass volume concentration of the stabilizer is 0.5-2 g/L.
The matrix is sheep serum, calf serum, human serum, or human plasma. The quality control mental drug concentrations are respectively as follows: 48-188ng/mL of duloxetine, 6-15ng/mL of haloperidol, 80-340ng/mL of ziprasidone, 40-132ng/mL of olanzapine, 308-856ng/mL of clozapine, 176-744ng/mL of N-norclozapine, 212-700ng/mL of quetiapine, 34-106ng/mL of risperidone and 24-96ng/mL of paliperidone.
The matrix is human plasma.
In a second aspect, the invention provides an application of the quality control product in mass spectrometric detection of the concentration of the psychotropic drug.
In a third aspect of the present invention, there is provided a quality control kit, comprising at least the above quality control materials in high and low concentrations, wherein the high concentration is between the upper therapeutic concentration limit and the warning concentration for each quality control psychotropic drug; the low concentration is that the concentration of each quality control mental medicament fluctuates by 10-20% above and below the lower limit of the treatment concentration.
The low concentration is duloxetine: 60 ± 12ng/mL, haloperidol: 7 +/-1 ng/mL, ziprasidone: 100 ± 20ng/mL, olanzapine: 47 + -7 ng/mL, clozapine: 380. + -.72 ng/mL, N-desmethylclozapine: 220 + -44 ng/mL, quetiapine: 260 ± 48ng/mL, risperidone: 40 plus or minus 6ng/mL, and 30 plus or minus 6ng/mL paliperidone.
The high concentration is duloxetine: 160 ± 28ng/mL, haloperidol: 13 ± 2ng/mL, ziprasidone: 300 + -40 ng/mL, olanzapine: 116 ± 16ng/mL, clozapine: 730. + -.126 ng/mL, N-desmethylclozapine: 620 ± 124ng/mL, quetiapine: 590 ± 110ng/mL, risperidone: 90 plus or minus 16ng/mL, and 80 plus or minus 16ng/mL paliperidone.
In a fourth aspect of the present invention, there is provided a method for producing the above quality control product, the method comprising the steps of:
(1) Dissolving 2,6-di-tert-butyl-4-methylphenol in ethanol, and adding the solution into a matrix to prepare a blank matrix solution with a certain concentration;
(2) Dissolving a proper amount of quality control psychotropic drugs in an organic solvent containing a stabilizing agent to respectively prepare solutions with required concentrations, and uniformly mixing the quality control psychotropic drug solutions;
(3) And (3) adding the quality control psychotropic drug solution in the step (2) into the blank matrix solution in the step (1) to obtain a quality control product solution with the required concentration, subpackaging and vacuum-drying.
The matrix is sheep serum, large bovine serum, human serum and human plasma; the weight volume concentration of 2,6-di-tert-butyl-4-methylphenol is 0.5-2 g/L.
The step (1) and the step (2) are not separated in sequence.
The matrix is human plasma.
Compared with a commercial psychotropic therapy drug monitoring non-constant quality control product (hereinafter referred to as 'Quilai quality control product') of Shanghai Quilai bioscience Co., ltd (www.china-qlab. Com), the quality control product for the liquid chromatography-tandem mass spectrometer developed by the team is compared with the quality control product for monitoring the commercial psychotropic therapy drug (hereinafter referred to as 'Quilai quality control product'), and the result shows that the quality control product has obvious advantages. The stability data in the quality control product specification of Kunlisha shows that the quality control product redissolving bottle can be stored for no more than 1 hour at room temperature, can be stored for only 1 day at the temperature of 2-8 ℃, can be stored for 90 days at the temperature of-70-20 ℃, but can not be repeatedly frozen and thawed. The quality control product of the invention can be stored for 5 years stably at-25 to-15 ℃ without ultralow temperature (minus 90 to minus 70 ℃) after being unpacked. The quality control product after redissolution can be repeatedly frozen and thawed for 5 times, can be stored for at least 8 hours (possibly longer) at room temperature, and can be stably stored for 14 days at the temperature of 2-8 ℃, and specific data can be obtained in the attached figure.
The invention discloses a human plasma freeze-dried agent quality control product containing 9 psychotropic drugs, which comprises a matrix solution, a mixed drug solution with a certain concentration and a stabilizer, wherein the concentration is divided into a low concentration and a high concentration, and the human plasma freeze-dried agent quality control product is characterized in that: the matrix liquid can be sheep serum, human plasma, human serum, etc.; the stabilizer comprises BHT and a solution mixed with blood plasma/blood serum according to a certain proportion; the 9 psychotropic drugs comprise duloxetine, haloperidol, ziprasidone, olanzapine, clozapine, N-norclozapine, quetiapine, risperidone, paliperidone. And the quality control product which is stable and easy to transport and store is prepared after vacuum freeze-drying treatment.
1. Part of the drugs (such as duloxetine, olanzapine and the like) contained in the quality control product prepared by the invention are extremely unstable at room temperature (see figure 1 in detail), and in order to facilitate storage and use, the applicant screens out a group of components capable of obviously improving the stability of the drugs and the proportion relationship thereof through investigation. The group of stabilizers can make the medicine more stable in transportation and storage, has remarkable advantages compared with commercial quality control products, and the specific data of related tests are shown in detail in table 1.
2. The accuracy and precision of the formula formed by adding the stabilizing agent into the plasma matrix are not affected and have no interference (see table 2 and figure 2 for details), so that the formula of the quality control product has no relative matrix effect and obvious interference with a real sample, and has good interoperability, and the product can be used for other biochemical detection methods besides a liquid chromatography-tandem mass spectrometry method.
3. The invention has the beneficial effects that: compared with other products, the invention has remarkable advantages, which are mainly shown in 2 aspects:
(1) The quality control product components of the stabilizer and the blood plasma according to a certain proportion are more stable for the storage of 9 anti-mental drugs, for example, the risk that olanzapine is easily adsorbed by plastic products is avoided, meanwhile, the ziprasidone is protected to be stable and not easy to degrade, and the low-concentration quality control product can be more stable by utilizing the formula. Through inspection, 9 medicaments in the quality control product freeze-dried powder can be stable for at least 5 years at the temperature of-25 to-15 ℃, can be stable for at least 14 days at the temperature of 2 to 8 ℃ after bottle opening and redissolution, can be repeatedly frozen and thawed for at least 5 times after redissolution, and can be stably placed for at least 8 hours at room temperature (25 ℃).
(2) The quality control product adopts human plasma as a matrix, and the accuracy, precision and uniformity of each medicine in the quality control product prepared by adding stabilizers in a certain proportion into different anticoagulant plasma and serum are examined by applying a common method of clinical mass spectrometry detection, and the results are better, so that the interoperability of the quality control product and the clinical detection method is better, and the requirement of clinical detection can be completely met. The process components have no related research report, and similar production processes of the same type of commercial quality control products have not been found.
Drawings
FIG. 1 stability of ziprasidone, olanzapine at 37 ℃ in plasma without added stabilizer;
a.37 deg.C stability of ziprasidone in plasma (No stabilizer)
B.stability of olanzapine in plasma at 37 deg.C (No stabilizer)
Figure 2 human blank plasma matrix map after addition of stabilizer BHT (no significant interference);
C. a duloxetine blank matrix diagram;
D. a haloperidol blank matrix map;
E. a ziprasidone blank matrix diagram;
F. clozapine blank matrix map;
G.N-norclozapine blank matrix map;
H. quetiapine blank matrigram;
I. a blank matrix map of olanzapine;
J. risperidone matrigel blank;
K. paliperidone blank matrix diagram.
Figure 3 stability of the drug product after addition of different stabilizers.
Stability of ziprasidone after adding stabilizer to plasma at L.25 deg.C
Stability of olanzapine after addition of stabilizer to plasma at M.25 deg.C
Detailed Description
In order to make those skilled in the art better understand the solution of the present invention, the following embodiments of the present invention are described clearly and completely, and it is obvious that the described embodiments are only a part of examples of the present invention, but not all embodiments.
The therapeutic concentration and the warning concentration are not included between the therapeutic concentration and the warning concentration. The concentrations according to the invention are, unless otherwise specified, mass-to-volume concentrations.
Example 1 matrix and stabilizer screening experiments
(1) Investigation of the substrate: the product considers sheep serum, large bovine serum, human serum and human plasma, and the performances of different matrixes added into the formula have no obvious difference.
(2) Selection of the stabilizer: the stabilizing agent selected by the invention comprises 0.5-2 g/L of tert-butyl hydroquinone (TBHQ), 0.5-2 g/L of 2,6-di-tert-butyl-4-methylphenol (BHT) and 0.5-2 g/L of Butyl Hydroxy Anisole (BHA). The stability results show that different stabilizers have a certain stabilizing effect on the drug, wherein the most preferred stabilizer is BHT (see figure 3 for details) in combination.
Example 2 production Process of quality control Material of the present invention
(1) Selection of drugs and concentrations: the 9 drugs are divided into duloxetine, haloperidol, ziprasidone, olanzapine, clozapine, N-norclozapine, quetiapine, risperidone, paliperidone. The concentrations are set to two concentrations, a low concentration being set near the lower therapeutic concentration limit of each drug and a high concentration being set between the upper therapeutic concentration limit and the guard concentration of the drug.
Preparation of Mixed working solution
1) Weighing a certain amount of analysis standard substance for each medicine, dissolving the analysis standard substance into 0.1-1 mg/mL single-standard stock solution by using methanol respectively, sucking a proper amount of the single-standard stock solution, preparing 100 multiplied mixed standard solution according to target concentration, and mixing the solution according to the ratio of 1:100 (volume ratio) adding the mixture into prepared blank plasma containing stabilizer BHT to prepare low-concentration and high-concentration quality control samples, respectively mixing uniformly and then subpackaging.
The low value Q1 and high value Q2 quality control preparation concentrations of each drug are as follows:
duloxetine: 60 + -12 ng/mL, 160 + -28 ng/mL, haloperidol: 7 +/-1 ng/mL, 13 +/-2 ng/mL, ziprasidone: 100 + -20 ng/mL, 300 + -40 ng/mL, olanzapine: 47 + -7 ng/mL, 116 + -16 ng/mL, clozapine: 380. + -.72 ng/mL, 730. + -.126 ng/mL, N-desmethylclozapine: 220 +/-44 ng/mL, 620 +/-124 ng/mL, quetiapine: 260 +/-48 ng/mL, 590 +/-110 ng/mL, risperidone: 40 plus or minus 6ng/mL, 90 plus or minus 16ng/mL, paliperidone 30 plus or minus 6ng/mL, 80 plus or minus 16ng/mL
(2) The preparation scheme is as follows: adding a small amount of BHT solution into animal or human biological matrixes which are qualified by screening, uniformly mixing to ensure that the BHT is fully dissolved to prepare matrixes containing 0.5-2 g/L of BHT, adding a certain amount of mixed working solution of 9 medicines, and controlling the volume of the added mixed working solution to be less than 5% of the final total volume to prepare quality control solution containing low and high concentrations which accord with the concentration range.
(3) And (3) a freeze-drying process: and (3) uniformly mixing the prepared quality control solution, subpackaging 1 mL/bottle, and drying in vacuum until the water content is below 3%.
Preparation of quality control product
1) Matrix: blank human plasma.
2) Adding a stabilizer: weighing a certain amount of BHT powder, dissolving the BHT powder with ethanol to prepare 200g/L BHT working solution, adding a small amount of BHT working solution into blank human plasma to enable the concentration to be between 0.5 and 2g/L, and uniformly stirring to obtain blank plasma matrix solution for later use.
3) Addition of analyte solution: adding the prepared low and high analyte solutions with set concentration into the blank plasma matrix solution respectively to prepare two quality control substance solutions with low value (low concentration) and high value (high concentration), stirring uniformly, subpackaging in small bottles with the specification of 1-3 mL respectively, and standing for pre-freezing at-25 to-15 ℃ for 24 hours.
4) And (3) freeze-drying and storing: vacuum freeze drying for 48 hr to obtain freeze dried quality control product, and storing at 2-8 deg.c.
Example 3 evaluation method of quality control Material of the invention
Uniformity: uniformity was examined according to the recommended method of CNAS-GL03 Performance verification sample uniformity and stability evaluation guidelines (hereinafter referred to as guidelines): randomly extracting more than or equal to 10 sets of quality control products, sucking for 2 times per bottle, and sampling samples according to a random sequence.
Stability: referring to the guide, 2 prepared freeze-dried powder quality control products with different concentrations are respectively placed according to different temperature conditions and different time nodes, 1mL of purified water is added at the temperature of minus 25 to minus 15 ℃ for redissolution, and the concentration values are simultaneously detected and compared by using a liquid mass spectrometry tandem method.
Table 1: freeze-dried quality control product and stability thereof after redissolution
Table 2: accuracy, precision and uniformity of 9 drugs in quality control (n = 20)
Note: and (4) carrying out statistical treatment on the results in the test by adopting a single-factor variance analysis method, and calculating that the F test value is less than the F critical value, so that no significant difference exists between the samples. And (3) judging that the uniformity of the sample can meet the requirement of capability verification if the standard deviation Ss of the nonuniformity among the samples is less than or equal to 0.3 sigma. As a result: the F-test values are all less than the F-critical value F α (0.05) =3.02, and the standard deviation Ss of the non-uniformity is ≦ 0.3 σ =6.0%, (where σ is equivalent to the total allowable error 20%).
As a result: the results show that the quality control product developed by the invention is uniform and stable, has long storage time, strong operability, no obvious matrix interference and good interoperability, can be used as a special quality control product for clinical mass spectrometry in different laboratories, and is expected to become a general quality control product for biochemical inspection.
Compared with a commercially available psychotropic drug monitoring non-constant quality control product (www.china-qlab. Com) of Shanghai Quilai Biotechnology Limited (www.china-qlab. Com), the quality control product disclosed by the invention has obvious advantages. The stability data in the quality control product specification of Quilai shows that the quality control product redissolution bottle can be stored for only 1 day at the temperature of 2-8 ℃, can be stored for 90 days at the temperature of-70-20 ℃, but can not be repeatedly frozen and thawed. The quality control product of the invention can be stored for 5 years stably at-25 to-15 ℃ without ultralow temperature (minus 90 to minus 70 ℃) after being unpacked. The quality control product after redissolution can be repeatedly frozen and thawed for 5 times, and can also be stably stored for 14 days at the temperature of 2-8 ℃.
Example 4 human plasma quality control kit
The kit contains quality control substance A freeze-dried powder, quality control substance B freeze-dried powder and a part of instruction.
Quality control product A freeze-dried powder: a plasma quality control freeze-drying agent containing 9 medicaments (duloxetine: 60 plus or minus 12ng/mL, haloperidol: 7 plus or minus 1ng/mL, ziprasidone: 100 plus or minus 20ng/mL, olanzapine: 47 plus or minus 7ng/mL, clozapine: 380 plus or minus 72ng/mL, N-norclozapine: 220 plus or minus 44ng/mL, quetiapine: 260 plus or minus 48ng/mL, risperidone: 40 plus or minus 6ng/mL, paliperidone: 30 plus or minus 6 ng/mL) and BHT of 0.5 to 2g/L.
Quality control product B freeze-dried powder: a plasma quality control freeze-drying agent containing 9 medicaments (duloxetine: 160 plus or minus 28ng/mL, haloperidol: 13 plus or minus 2ng/mL, ziprasidone: 300 plus or minus 40ng/mL, olanzapine: 116 plus or minus 16ng/mL, clozapine: 730 plus or minus 126ng/mL, N-norclozapine: 620 plus or minus 124ng/mL, quetiapine: 590 plus or minus 110ng/mL, risperidone: 90 plus or minus 16ng/mL, paliperidone 80 plus or minus 16 ng/mL) and 0.5-2 g/L BHT.
The using method comprises the following steps: at room temperature (15-25 ℃), in an environment without air circulation or direct sunlight, carefully opening a bottle cap of a quality control product, accurately adding 1mL of deionized water or distilled water, covering the bottle cap, standing until the product is completely dissolved (about 20 minutes), slightly inverting and rotating to mix uniformly, and sampling and measuring after the product is fully mixed. If the quality control product needs to be repeatedly frozen and thawed for use after redissolving, the bottle cap is immediately covered and put back into a refrigerator for storage after sampling is finished each time, and the bottle cap is placed at room temperature for fully thawing and is uniformly mixed before next use for sampling and detecting.
Finally, it should be noted that the above embodiments are merely exemplary embodiments adopted to illustrate the principle of the present invention, but the present invention is not limited thereto. It will be apparent to those skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope of the invention, and these changes and modifications are to be considered as within the scope of the invention.
Claims (10)
1. A quality control product is characterized by comprising quality control psychotropic drugs, a stabilizer and a matrix, wherein the drugs, the stabilizer and the matrix are mixed to prepare freeze-dried powder; the quality control psychotropic drugs comprise duloxetine, haloperidol, ziprasidone, olanzapine, clozapine, N-norclozapine, quetiapine, risperidone and paliperidone; the stabilizer is 2,6-di-tert-butyl-4-methylphenol.
2. The quality control product of claim 1, wherein the mass volume concentration of the stabilizer is 0.5-2 g/L.
3. The quality control product according to claim 1, wherein the substrate is sheep serum, large bovine serum, human serum, or human plasma.
4. The quality control product according to claim 1, wherein the concentration of the quality control psychotropic drugs is respectively as follows: 48-188ng/mL of duloxetine, 6-15ng/mL of haloperidol, 80-340ng/mL of ziprasidone, 40-132ng/mL of olanzapine, 308-856ng/mL of clozapine, 176-744ng/mL of N-norclozapine, 212-700ng/mL of quetiapine, 34-106ng/mL of risperidone and 24-96ng/mL of paliperidone.
5. Use of the quality control substance according to any one of claims 1-4 in mass spectrometric testing of psychotropic drug concentrations.
6. A quality control kit comprising at least a high concentration and a low concentration of the quality control substance according to any one of claims 1 to 4, wherein the high concentration is between the therapeutic upper concentration limit and the alert concentration for each quality control psychotropic drug; the low concentration is that the concentration of each quality control mental medicament fluctuates by 10-20% above and below the lower limit of the treatment concentration.
7. The quality control kit according to claim 6, wherein the low concentration is duloxetine: 60 ± 12ng/mL, haloperidol: 7 +/-1 ng/mL, ziprasidone: 100 ± 20ng/mL, olanzapine: 47 + -7 ng/mL, clozapine: 380. + -.72 ng/mL, N-desmethylclozapine: 220 + -44 ng/mL, quetiapine: 260 ± 48ng/mL, risperidone: 40 plus or minus 6ng/mL, and 30 plus or minus 6ng/mL paliperidone.
8. The quality control kit according to claim 8, wherein the high concentration is duloxetine: 160 ± 28ng/mL, haloperidol: 13 ± 2ng/mL, ziprasidone: 300 +/-40 ng/mL, olanzapine: 116 ± 16ng/mL, clozapine: 730. + -.126 ng/mL, N-desmethylclozapine: 620 ± 124ng/mL, quetiapine: 590 ± 110ng/mL, risperidone: 90 plus or minus 16ng/mL, and 80 plus or minus 16ng/mL paliperidone.
9. The method for preparing a quality control material according to claim 1, comprising the steps of:
(1) Dissolving 2,6-di-tert-butyl-4-methylphenol in ethanol, and adding the solution into a matrix to prepare a blank matrix solution with a certain concentration;
(2) Dissolving a proper amount of quality control psychotropic drugs in an organic solvent containing a stabilizer to prepare solutions with required concentrations respectively, and uniformly mixing the quality control psychotropic drug solutions;
(3) And (3) adding the quality control psychotropic drug solution in the step (2) into the blank matrix solution in the step (1) to obtain a quality control product solution with the required concentration, subpackaging and vacuum-drying.
10. The method for preparing a quality control product according to claim 9, wherein the substrate is sheep serum, large bovine serum, human serum, or human plasma; the mass volume concentration of 2,6-di-tert-butyl-4-methylphenol is 0.5-2 g/L.
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