Morphine detection quality control agent and preparation method thereof

Abstract

The invention relates to the technical field of medicine preparation, in particular to a morphine detection quality control agent and a preparation method. The morphine detection quality control agent comprises a positive quality control agent and a negative quality control agent, the positive quality control agent is prepared from compound licorice tablets, and the negative quality control agent is prepared from licorice tablets. According to the preparation method disclosed by the invention, the long-term stable negative and positive property control agent can be obtained by simply grinding, dissolving and storing paired medicines such as liquorice tablets and compound liquorice tablets which are sold in the market and easy to obtain as raw materials. The kit can be taken and used at any time in daily life, can achieve the purpose of quality control on daily detection without complex operation, and has the characteristics of simplicity in operation and convenience in preparation. The compound licorice tablets and licorice tablets can be purchased in drugstores or hospitals and are convenient to obtain.

Description

Technical Field

[0001] The invention relates to the technical field of drug preparation, in particular to a morphine detection quality control agent and a preparation method thereof. Background Art

[0002] Morphine is a powerful analgesic drug that has the risk of addiction and abuse and needs to be used medically under strict restrictions.

[0003] At present, the detection of morphine mainly involves collecting samples such as urine, blood, saliva, and hair, and using antibody-antigen specific binding reaction and immunomembrane chromatography technology (colloidal gold method), high performance liquid chromatography or liquid chromatography-tandem mass spectrometry analysis. Since urine samples are relatively non-invasive, antibody-antigen specific binding reaction and immunomembrane chromatography technology (colloidal gold method) are simple to operate and have a low technical threshold, this detection method is widely used for large-scale screening and daily monitoring.

[0004] Quality control refers to the control and management of the quality of products or services through certain methods and means during the experiment or production process to ensure that they meet the predetermined standards and requirements. At present, the use of morphine standards or morphine preparations is restricted. Laboratories that only use the colloidal gold method for morphine testing have no channels to obtain morphine standards or morphine preparations, resulting in the lack of negative and positive quality control agents for testing. Note: When the "C" band of the indicator strip in the gold label method kit is positive, it only means that the sample addition is effective, and does not mean that the morphine substance test is negative or positive.

[0005] Quality control is particularly important in scientific research and experiments. Experiments without quality control are more risky, mainly because they may lead to inaccurate data, unreliable results, and even wrong conclusions due to experimental errors.

[0006] In view of the above problems, there is an important motivation to develop easily available negative and positive quality control agents for morphine detection. Summary of the invention

[0007] Based on the experience of morphine testing, it was found that some morphine-positive patients had no morphine medication experience or drug abuse history. After inquiring about the patients' other medication or dietary experience, it was found that some patients had used compound licorice tablets.

[0008] After consulting the drug instructions and literature search, taking the compound licorice tablets produced by Sinopharm Group as an example, it was found that the compound licorice tablets contained 4 mg of opium powder, which contained about 10% anhydrous morphine (C 17 H 19 NO 3 ), the instructions show that each tablet contains 0.36-0.44mg of anhydrous morphine; at the same time, it was found that the main difference between licorice tablets and compound licorice tablets is that licorice tablets do not contain opium powder, that is, morphine. Taking the licorice tablets of Caoshanhu Group as an example, the instructions show that each tablet weighs 0.2g.

[0009] Therefore, the first object of the present invention is to provide a morphine detection quality control agent, which includes a positive quality control agent and a negative quality control agent. The positive quality control agent is prepared from compound licorice tablets, and the negative quality control agent is prepared from licorice tablets.

[0010] The second object of the present invention is to provide a method for rapidly preparing a morphine detection quality control agent, the steps comprising:

[0011] A. Preparation and testing of negative quality control agent solution:

[0012] A1 weigh 0.136g of licorice powder into a beaker;

[0013] A2: Add 5 mL of distilled water to each beaker to dissolve the licorice powder;

[0014] A3 Transfer the above solution into a 10mL volumetric flask and dilute to 10mL with distilled water;

[0015] A4 test: Take the morphine test reagent out of the aluminum foil bag and place it on a clean, flat surface. Use a plastic dropper to vertically add 3 drops of distilled water licorice tablet solution to the sample (S) wells. Let it stand for 5 minutes and read the results within 10 minutes. The results should be negative.

[0016] Preparation and testing of B positive quality control agent solution:

[0017] B1 weigh 0.136g of compound licorice tablet powder into a beaker;

[0018] Add 5 mL of distilled water to beaker B2 to dissolve the compound licorice tablet powder;

[0019] B3 Transfer the solution to a 10 mL volumetric flask and dilute to 10 mL with distilled water;

[0020] B4 test: Take 1 portion of morphine test reagent, take it out of the aluminum foil bag, place it on a clean and flat table, use a plastic dropper to vertically add 3 drops of distilled water compound licorice tablet solution to the sample (S) well, let it stand for 5 minutes, read the result within 10 minutes, and the result is positive;

[0021] Preparation of gradient concentrations of B5 positive quality control agents: According to the average morphine content of compound licorice tablets of 0.40 mg / tablet, 1 tablet of compound licorice tablet is used to prepare 10 mL of morphine solvent, and the obtained theoretical morphine concentration is: 0.4 mg / 10 mL = 0.04 mg / mL = 40000 ng / mL. The threshold value of morphine detection reagent for detecting morphine is 300 ng / mL. Distilled water is used to prepare quality control agents at various concentration levels.

[0022] The beneficial technical effect of the present invention is that the present invention uses commercially available paired medicines licorice tablets and compound licorice tablets as raw materials, and can obtain long-term stable negative and positive quality control agents through simple grinding, dissolution and storage. It can be taken and used daily without complicated operations, and can meet the purpose of quality control for daily testing, and has the characteristics of simple operation and convenient preparation. Compound licorice tablets and licorice tablets can be purchased in pharmacies or hospitals, and are relatively convenient to obtain. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0024] Figure 1 This is the test result of the negative quality control agent morphine in Example 1.

[0025] Figure 2 These are the test results of morphine at various concentrations of the positive quality control agent in Example 1.

[0026] Figure 3 This is the test result of the positive quality control agent morphine in Example 1.

[0027] Figure 4 This is the morphine test result of the positive quality control agent in Example 2 after 60 days of warranty.

[0028] Figure 5 This is the morphine test result of the negative quality control agent in Example 2 after 60 days of warranty. DETAILED DESCRIPTION

[0029] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] Example 1

[0031] A method for rapidly preparing a quality control agent for morphine detection, wherein the quality control agent includes a positive quality control agent and a negative quality control agent, and the steps include:

[0032] A. Preparation and testing of negative quality control agent solution:

[0033] A1 weigh 0.136g of licorice powder into a beaker;

[0034] A2: Add 5 mL of distilled water to each beaker to dissolve the licorice powder;

[0035] A3 Transfer the above solution into a 10mL volumetric flask and dilute to 10mL with distilled water;

[0036] A4 test: Take the morphine test reagent out of the aluminum foil bag and place it on a clean, flat surface. Use a plastic dropper to vertically add 3 drops of distilled water licorice tablet solution to the sample (S) wells. Let it stand for 5 minutes and read the results within 10 minutes. If the result is negative, the result is as follows: Figure 1 shown.

[0037] Preparation and testing of B positive quality control agent solution:

[0038] B1 weigh 0.136g of compound licorice tablet powder into a beaker;

[0039] Add 5 mL of distilled water to beaker B2 to dissolve the compound licorice tablet powder;

[0040] B3 Transfer the solution to a 10 mL volumetric flask and dilute to 10 mL with distilled water;

[0041] B4 test: Take 1 portion of morphine test reagent, take it out of the aluminum foil bag, place it on a clean and flat surface, use a plastic dropper to vertically add 3 drops of distilled water compound licorice tablet solution to the sample addition (S) well, let it stand for 5 minutes, read the result within 10 minutes, and the result is positive (such as Figure 2 shown);

[0042] B5 Positive quality control agent gradient concentration preparation: According to the average morphine content of compound licorice tablets of 0.40 mg / tablet, use 1 compound licorice tablet to prepare 10 mL of morphine solvent, and the obtained morphine theoretical concentration is: 0.4 mg / 10 mL = 0.04 mg / mL = 40000 ng / mL. The threshold value of morphine detection reagent for detecting morphine is 300 ng / mL. Use distilled water to prepare quality control agents at various concentration levels. The inspection results are as follows: Figure 3 shown.

[0043] The configuration ratio and theoretical concentration are shown in the following table.

[0044]

[0045] Example 2

[0046] Quality control agent for performance verification

[0047] 1. Verification of compliance with expected concentration:

[0048] The above-mentioned quality control agents of each concentration were used to detect morphine using the colloidal gold method.

[0049] The results on day 0 showed that samples with expected morphine concentrations greater than or equal to 100 ng / mL were all positive for morphine; samples with expected morphine concentrations less than or equal to 80 ng / mL and licorice tablet solutions were negative for morphine using the colloidal gold method.

[0050] 2. Stability verification:

[0051] Dispense 200uL of the above compound licorice tablet solutions and licorice tablet solutions of different concentrations into screw-capped tubes and mark them.

[0052] Storage conditions: Store the above packaged samples at 2-8℃, 20-30℃, and below -20℃ respectively.

[0053] Shelf life verification:

[0054] On day 0, 2, 5, 10, 15, 20, 25, 30, 35, 40, 50, and 60 (the positive control agent morphine test results are as follows Figure 4 As shown, the negative quality control agent morphine test results are as follows Figure 5 After that, samples with different concentrations and storage conditions were rewarmed and tested.

[0055] From 0 to 30 days, the test results were stable. For samples with expected morphine concentrations greater than or equal to 100 ng / mL, the morphine test results were all positive. For samples with expected morphine concentrations less than or equal to 80 ng / mL and licorice tablet solutions, the morphine test results using the colloidal gold method were negative. From 30 to 50 days, for samples with expected morphine concentrations less than or equal to 200 ng / mL, the morphine test results gradually turned weakly positive and negative. From 0 to 60 days, for samples with different storage conditions and expected morphine concentrations greater than or equal to 400 ng / mL, the morphine test results of licorice tablet solutions were all positive.

[0056] In summary, the morphine negative and positive quality control agents obtained by dissolving drugs in distilled water have relatively stable properties and are less affected by storage conditions. As the storage time increases, the morphine concentration gradually decreases. However, when stored for 60 days, the stability can still meet the quality control requirements, that is, the threshold value (300ng / mL) of morphine detection reagent (colloidal gold method) for detecting morphine is near, and it is expected that the compound licorice tablet solution with a morphine concentration of more than 400ng / mL can remain positive for a long time.

[0057] Finally, it should be noted that the above embodiments are only used to illustrate rather than limit the technical solutions of the present invention. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that the present invention can still be modified or replaced by equivalents. Any modification or partial replacement that does not depart from the spirit and scope of the present invention should be included in the scope of the claims of the present invention.

Claims

1. A quality control agent for morphine detection, characterized in that: The morphine detection quality control agent includes a positive quality control agent and a negative quality control agent. The positive quality control agent is prepared from compound licorice tablets, and the negative quality control agent is prepared from licorice tablets.

2. A method for rapidly preparing the morphine detection quality control agent according to claim 1, characterized in that the steps include: A. Preparation and testing of negative quality control agent solution: A1 weigh 0.136g of licorice powder into a beaker; A2: Add 5 mL of distilled water to each beaker to dissolve the licorice powder; A3 Transfer the above solution into a 10mL volumetric flask and dilute to 10mL with distilled water; A4 test: Take the morphine test reagent out of the aluminum foil bag and place it on a clean, flat surface. Use a plastic dropper to vertically add 3 drops of distilled water licorice tablet solution to the sample (S) well, let it stand for 5 minutes, and read the results within 10 minutes. Preparation and testing of B positive quality control agent solution: B1 weigh 0.136g of compound licorice tablet powder into a beaker; Add 5 mL of distilled water to beaker B2 to dissolve the compound licorice tablet powder; B3 Transfer the solution to a 10 mL volumetric flask and dilute to 10 mL with distilled water; B4 test: Take 1 portion of morphine test reagent, take it out of the aluminum foil bag, place it on a clean and flat table, use a plastic dropper to vertically add 3 drops of distilled water compound licorice tablet solution to the sample addition (S) well, let it stand for 5 minutes, and read the result within 10 minutes; Preparation of gradient concentrations of B5 positive quality control agents: According to the average morphine content of compound licorice tablets of 0.40 mg / tablet, 1 tablet of compound licorice tablet is used to prepare 10 mL of morphine solvent, and the obtained theoretical morphine concentration is: 0.4 mg / 10 mL = 0.04 mg / mL = 40000 ng / mL. The threshold value of morphine detection reagent for detecting morphine is 300 ng / mL. Distilled water is used to prepare quality control agents at various concentration levels.

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