Kit for detecting concentration of anticoagulant drug in plasma
By designing a reagent rack inside the kit and using guide holes and limiting holes to fix the container, the problems of instability during transportation and easy damage during use are solved, ensuring the stability of the container and the convenience of use.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- WUXI APPTEC ZK (SUZHOU) BIOSCIENCE CO LTD
- Filing Date
- 2024-12-31
- Publication Date
- 2026-05-12
AI Technical Summary
Existing reagent kits for detecting anticoagulant concentrations in plasma have unstable containers during transportation, making them prone to being knocked over or confused during use, and the contents inside are easily lost.
A reagent kit with a reagent rack was designed. The reagent rack has a guide layer, a lower limit layer and an upper limit layer to fix the containers of extract, quality control products and calibrators, so as to avoid removing the containers separately. The guide hole and the limit hole ensure the stability of the containers.
It ensures the stability of the container during transportation, preventing it from being overturned or confused, making it less likely for the contents to be lost, and simplifying the usage process.
Smart Images
Figure CN224231722U_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of reagent kit technology, and in particular to a reagent kit for detecting the concentration of anticoagulant drugs in plasma. Background Technology
[0002] Anticoagulants are drugs that prevent blood clotting by interfering with certain steps of the body's physiological coagulation process. They are mainly used to prevent thrombus formation or the further development of existing thrombi. The mechanism of action of anticoagulants is to reduce the level of coagulation factors or antagonists in the blood to prevent the amplification of the coagulation effect, alleviate the hypercoagulable state, and avoid the formation of fibrin emboli. The key to successful anticoagulation therapy lies in effectively inhibiting pathological coagulation activation while maintaining the body's physiological hemostatic ability.
[0003] Typically, routine pharmacokinetic (PK) or pharmacodynamic (PD) laboratory monitoring is not required when using novel oral anticoagulants at fixed clinical doses. However, clinical studies have shown that drug monitoring is necessary in certain populations, such as the elderly, individuals with abnormal weight, those using medications that affect drug-metabolizing enzymes, and those with impaired renal function or poor response. Furthermore, monitoring is also necessary for patients using novel direct oral anticoagulants when special interventions are required or in certain emergency situations (such as bleeding, acute stroke, trauma, or surgery) where the anticoagulation effect needs to be assessed to guide subsequent treatment.
[0004] Currently, common detection methods for anticoagulants include enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay (CLI), and high-performance liquid chromatography (HPLC). Immunological methods often suffer from cross-reactivity due to antibody specificity issues, leading to incorrect estimations of drug concentrations, erroneous analytical results, and potential clinical misdiagnosis. In contrast, liquid chromatography-tandem mass spectrometry (LC-MS / MS) determines the drug's intrinsic concentration, providing a more accurate picture of the relationship between drug concentration, efficacy, and adverse reactions. Furthermore, LC-MS / MS offers advantages such as short analysis time, rapid sample processing, high specificity, high accuracy, high sensitivity, and low cost.
[0005] LC-MS / MS technology has become the primary method and trend for monitoring blood drug concentrations in patients. To facilitate detection and simplify the testing process, a reagent kit for detecting anticoagulant drug concentrations in plasma needs to be developed. Existing reagent kits generally include a box and an inner liner. The inner liner has reagent wells to hold containers (or reagent tubes) containing solvent, while the instruction manual and other non-container items are placed on top of the containers (or reagent tubes). However, because the inner liner is generally located at the bottom of the kit and its thickness is less than half the height of the kit, the containers (or reagent tubes) are mostly unsecured, leading to instability during transportation. During use, the instruction manual and other non-container items need to be removed and placed on the work surface, or, as needed, separate containers can be removed and placed on the work surface or reagent rack. After use, the containers are then placed back into the kit. The instruction manual and other non-container items are easily lost after being separated from the kit. When containers are placed on the work surface, accidental opening can cause them to tip over, spilling solvent and making the experiment impossible. If placed on a reagent rack, an additional rack is required. In addition, there is a certain possibility of confusion when containers are taken out and put back. Utility Model Content
[0006] The technical problem to be solved by this invention is to provide a reagent kit for detecting the concentration of anticoagulant drugs in plasma, which ensures the stability of the container during transportation and eliminates the need to remove the container separately during use, thus avoiding spillage or confusion.
[0007] To solve the above-mentioned technical problems, the present invention provides a reagent kit for detecting the concentration of anticoagulants in plasma, comprising a box and a reagent rack placed inside the box. The reagent rack is matched with the internal volume of the box for accommodating extraction solution containers, quality control containers, and calibrator containers. The reagent rack includes:
[0008] A guide layer is provided near the top of the reagent rack, and the guide layer has guide holes for the extraction liquid container, the quality control container, and the calibrator container;
[0009] A lower limiting layer is disposed at the bottom of the reagent rack, and the lower limiting layer has lower limiting holes corresponding to the positions of the guide holes of the extraction liquid container, the guide holes of the quality control container, and the guide holes of the calibrator container, respectively.
[0010] An upper limit layer is disposed between the guide layer and the lower limit layer, and the upper limit layer has upper limit holes corresponding to the positions of the guide holes of the extract container, the guide holes of the quality control container and the guide holes of the calibrator container respectively;
[0011] A side wall receiving groove is provided on the side wall of the reagent rack facing the side wall of the box.
[0012] Preferably, the diameter of the guide hole in the extract container is larger than the diameter of the guide hole in the quality control container;
[0013] The diameter of the guide hole in the quality control container is larger than that in the guide hole in the calibrator container.
[0014] Preferably, labels are provided near the guide holes of the extract container, the quality control container, and the calibrator container.
[0015] Preferably, the lower limiting layer is made of sponge, and the diameter of the lower limiting hole is smaller than the diameter of its corresponding container.
[0016] Preferably, the upper limit layer is made of cardboard, the diameter of the upper limit hole is larger than the diameter of the corresponding container, and an elastic sheet extending from the hole wall to the center of the hole is formed circumferentially around the upper limit hole.
[0017] Preferably, there are multiple quality control containers, each used to hold blank quality control samples and quality control samples of different concentrations.
[0018] Preferably, there are multiple calibrator containers, each used to hold multiple calibrators of different concentrations.
[0019] Preferably, the box body is provided with a cover.
[0020] This invention provides a reagent kit for detecting anticoagulant concentrations in plasma. The extraction solution container, quality control container, and calibrator container are placed directly on the reagent rack. During use, the entire reagent rack is removed; individual containers do not need to be taken out separately, avoiding confusion and the risk of spillage. Furthermore, the bottoms of the extraction solution container, quality control container, and calibrator container are limited and fixed by lower limit holes in the lower limit layer, and the middle portions are limited and fixed by elastic sheets located within upper limit holes in the upper limit layer. Additionally, guide holes in the guide layer also provide some limiting and fixing functions, thus ensuring the stability of each container within the reagent kit. Moreover, the included non-container items, such as the instruction manual, are less likely to be lost. Attached Figure Description
[0021] To more clearly illustrate the technical solution of this utility model, the drawings used in this utility model will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this utility model. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.
[0022] Figure 1 This is a schematic diagram of an embodiment of the reagent kit for detecting the concentration of anticoagulant drugs in plasma according to the present invention;
[0023] Figure 2 This is a schematic diagram of the reagent rack of an embodiment of the reagent kit for detecting the concentration of anticoagulant drugs in plasma according to this utility model;
[0024] In the diagram, 1-box body; 11-lid body; 2-reagent rack; 21-guide layer; 22-lower limit layer; 23-upper limit layer; 24-side wall receiving groove; 25-label; 211-extraction liquid container guide hole; 212-quality control product container guide hole; 213-calibrator product container guide hole; 221-lower limit hole; 231-upper limit hole; 2311-elastic sheet. Detailed Implementation
[0025] The technical solutions of this utility model will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this utility model. All other embodiments obtained by those skilled in the art based on the embodiments of this utility model without creative effort are within the scope of protection of this utility model.
[0026] Example 1: Reagent Kit for Detecting Anticoagulant Drug Concentration in Plasma
[0027] refer to Figure 1 and Figure 2 This invention discloses a reagent kit for detecting anticoagulant drug concentration in plasma, comprising a housing and a reagent rack placed within the housing. The reagent rack is matched to the internal volume of the housing for accommodating extraction solution containers, quality control containers, and calibrator containers. The reagent rack includes:
[0028] A guide layer is provided near the top of the reagent rack, and the guide layer has guide holes for the extraction liquid container, the quality control container, and the calibrator container;
[0029] A lower limiting layer is disposed at the bottom of the reagent rack, and the lower limiting layer has lower limiting holes corresponding to the positions of the guide holes of the extraction liquid container, the guide holes of the quality control container, and the guide holes of the calibrator container, respectively.
[0030] An upper limit layer is disposed between the guide layer and the lower limit layer, and the upper limit layer has upper limit holes corresponding to the positions of the guide holes of the extract container, the guide holes of the quality control container and the guide holes of the calibrator container respectively;
[0031] A side wall receiving groove is provided on the side wall of the reagent rack facing the side wall of the box.
[0032] In this embodiment of the invention, the reagent kit has a built-in reagent rack. The extraction solution container, quality control container, and calibrator container are preferably cylindrical (existing designs can be used, so they are not shown) and are placed on the reagent rack. When in use, the entire reagent rack is removed from the reagent kit and placed on the operating table. The container lid is opened, and liquid is taken from the required container as needed. There is no need to remove the containers from the reagent rack separately, effectively avoiding the risk of confusion or spillage. At the same time, after each container is placed on the reagent rack, the bottom of the container is limited and fixed by the lower limiting hole, and the middle of the container is limited and fixed by the upper limiting hole. Each guide hole also plays a certain limiting role on the upper part of the corresponding container, thereby effectively ensuring the stability of the container in the reagent kit and facilitating transportation. Meanwhile, non-container items such as the instruction manual are placed in the side wall receiving slot. When needed, they are taken out for use and placed back in the side wall receiving slot after use. When not in use, they are always placed in the side wall receiving slot, making them less likely to be lost. The side wall receiving slot is set on the side wall of the reagent rack by conventional means such as buckles. It should be noted that after the container is placed on the reagent rack, the height from the bottom of the reagent rack to the top of the container is the same as the height of the reagent kit. This facilitates the reagent kit to limit the container's position in the height direction (generally the vertical direction), ensuring the container's stability. The sum of the lengths of the reagent rack and the side wall receiving slots is the same as the length of the reagent kit, facilitating the reagent kit to limit the length of the reagent rack and the side wall receiving slots. The width of the reagent rack is the same as the width of the reagent kit, facilitating the reagent kit to limit the width of the reagent rack. It should also be noted that in this embodiment, the number of upper limit holes, lower limit holes, and guide holes is the same as the number of guide holes, and their positions correspond, facilitating the placement of each container. Positional correspondence generally refers to vertical alignment; for example, the center position of the guide hole of the extraction liquid container and the center positions of its corresponding upper limit hole and lower limit hole are aligned vertically.
[0033] In one specific embodiment, the aperture of the guide hole in the extract container is larger than that in the quality control container; the aperture of the guide hole in the quality control container is larger than that in the calibrator container. Understandably, the amount of extract is generally larger, followed by the amount of quality control, and then the amount of calibrator. Therefore, it is preferable that the extract container is larger (generally a cylindrical container, i.e., with a larger aperture), followed by the aperture of the quality control container guide hole, and then the aperture of the calibrator container guide hole is the smallest. It should be noted that the aperture of the extract container guide hole is slightly larger than that of the extract container to facilitate its placement; similarly, the aperture of the quality control container guide hole is slightly larger than that of the quality control container, and the aperture of the calibrator container guide hole is slightly larger than that of the calibrator. It should be noted that in this specific embodiment, "slightly larger" means that the container can pass through smoothly, for example, the aperture difference is between 1-3 mm.
[0034] In one specific embodiment, labels are provided near the guide holes of the extraction liquid container, the quality control container, and the calibrator container. It is understood that this specific embodiment is to further distinguish the containers; for example, both the quality control and calibrators are reagents of multiple different concentrations. To better differentiate and more quickly identify them, each reagent is labeled, facilitating rapid identification and use by the operator and improving detection efficiency.
[0035] In one specific embodiment, the lower limiting layer is made of sponge, and the diameter of the lower limiting hole is smaller than the diameter of its corresponding container. Preferably, the upper limiting layer is made of cardboard, the diameter of the upper limiting hole is larger than the diameter of its corresponding container, and an elastic sheet extending from the hole wall to the center of the hole is formed circumferentially around the upper limiting hole. In this specific embodiment, the lower limiting layer, for example, uses the same material as a conventional inner liner, which has a certain shock absorption effect. At the same time, since the diameter of the lower limiting hole is smaller than the diameter of its corresponding container, it plays a good stabilizing role for the container. The lower limiting layer can be placed directly on the bottom surface of the reagent rack, for example. Using cardboard for the upper limiting layer can reduce manufacturing costs to a certain extent. In order to achieve the limiting effect, the diameter of the upper limiting hole is generally larger than the diameter of its corresponding container. An elastic sheet (triangular cardboard) extending towards the center is formed circumferentially around the upper limiting hole. The vertices of the triangular cardboard converge at the center or converge to form a circle smaller than the diameter of the container. In this way, when the container passes through the upper limiting hole, the elastic sheet deforms towards the lower limiting layer, generating a certain elastic force, thereby limiting and fixing the container. The upper limit layer is installed between the two side walls of the reagent rack using conventional methods such as clips.
[0036] In one specific embodiment, the number of quality control containers is multiple, each used to hold blank quality control samples and quality control samples of different concentrations. Preferably, the number of calibrator containers is multiple, each used to hold multiple calibrators of different concentrations. For example, the quality control samples include blank quality control samples, and low-concentration, medium-concentration, and high-concentration quality control samples; low, medium, and high concentrations are relative and do not represent specific concentration ranges. For example, the calibrators include six solvents of different concentrations.
[0037] In one specific embodiment, the box body is provided with a lid. It is understood that the lid is preferably located at the top of the box body.
[0038] Example 2: Preparation and Method Validation of a Kit for Detecting Anticoagulant Drug Concentration in Plasma
[0039] 1. Instrument: Ultra-high performance liquid chromatography-tandem mass spectrometry system (model: AB Sciex 4500MD).
[0040] 2. Reagents: Anticoagulant standards ticagrelor, ticagrelor metabolites, rivaroxaban, dabigatran, aspirin, apixaban, warfarin, clopidogrel (Manhag (Shanghai) Biotechnology Co., Ltd., purity ≥95%); methanol (chromatographic grade, Merck, Germany); formic acid (chromatographic grade, Merck, Germany); bovine serum albumin (Sigma).
[0041] 3. Experimental conditions:
[0042] Chromatographic conditions: Column is ACQUITY HSS C18 SB 1.8μm, 2.5mm×50mm, 1.8μm; mobile phase: 0.1% formic acid-water solution (A), 0.1% formic acid-acetonitrile solution (B); flow rate: 0.6mL / min, column temperature: 40℃, injection volume: 5μL. Gradient elution: 80% A from 0 to 0.5 min, 80% A → 40% A from 0.5 to 3.8 min, 40% A → 2% A from 3.8 to 3.9 min, 2% A from 3.9 to 4.2 min, 2% A → 80% A from 4.2 to 4.21 min, 80% A from 4.21 to 4.5 min.
[0043] Mass spectrometry conditions: Electrospray ionization (ESI) source, positive ion mode, scan type multiple reaction monitoring (MRM) mode, CUR: 30 psi, source temperature: 600 °C, electrospray voltage: 4500 V, GAS1: 50 pso, GAS2: 50 psi. Anticoagulation mass spectrometry information is shown in Table 1.
[0044] For detailed anticoagulation mass spectrometry parameters, please refer to Table 1.
[0045] Table 1
[0046] Q1 Q3 Dwell Time ID DP CE 472.3 289.3 15 Dabiga Group 80 37 178.9 136.8 15 aspirin 40 9 321.9 212.1 15 Clopidogrel 50 23 309.1 250.9 15 warfarin 50 12 436.2 144.9 15 Livarsaban 110 40 460.2 443.4 15 Apixaban 90 25 523.3 153.1 15 Tigrose 90 50 479.4 153.0 15 Ticagrelor metabolites 18 39
[0047] 4. Preparation of calibrators and quality control samples
[0048] Calibration preparation: Weigh an appropriate amount of anticoagulation standard (TLC) into a volumetric flask and dilute to volume with methanol to obtain an anticoagulation stock solution. Dilute the anticoagulation stock solution with methanol to obtain a secondary anticoagulation stock solution. Dilute the secondary anticoagulation stock solution with bovine serum albumin to obtain a high-concentration anticoagulation matrix solution. Mix an appropriate amount of methanol thoroughly with bovine serum albumin to obtain a blank matrix solution (blank quality control). Then, obtain calibration point C6 by weighing and diluting the above high-concentration matrix solution and the blank matrix solution. Obtain calibration points C1 to C5 by weighing and diluting calibration point C6 and the blank matrix solution, thus obtaining calibrators C1 to C6.
[0049] Preparation of quality control samples: The preparation method is the same as that for calibrators, resulting in low-concentration quality control samples (LQC), medium-concentration quality control samples (MQC), and high-concentration quality control samples (HQC).
[0050] In one specific implementation, the concentrations of the calibrators and quality control samples are shown in Table 2:
[0051] Table 2
[0052]
[0053] 5. Product process verification
[0054] This product is a mass spectrometry quantitative detection kit. Within a certain concentration range, the instrument response is positively correlated with the concentration. Therefore, this product is used to evaluate the deviation of the prepared product calibrators and quality control samples. The deviation of the preparation process from the theoretical concentration and the linear correlation were verified, and the verification results are shown in Table 3.
[0055] Table 3
[0056]
[0057] The acceptable criteria are: linear correlation coefficient r ≥ 0.9900, and linear deviation within ±15%.
[0058] The results in Table 3 show that the processes for product calibrators and quality control samples have been verified, with a linear correlation coefficient r ≥ 0.9900 and a linear deviation within ±15%. This meets the expected product requirements.
[0059] The above description is only a preferred embodiment of the present utility model and is not intended to limit the present utility model. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present utility model should be included within the scope of protection of the present utility model.
Claims
1. A reagent kit for detecting the concentration of anticoagulant drugs in plasma, characterized in that, The package includes a housing and a reagent rack disposed within the housing, the reagent rack being matched to the internal volume of the housing for accommodating extraction solution containers, quality control containers, and calibrator containers, the reagent rack comprising: A guide layer is provided near the top of the reagent rack, and the guide layer has guide holes for the extraction liquid container, the quality control container, and the calibrator container; A lower limiting layer is disposed at the bottom of the reagent rack, and the lower limiting layer has lower limiting holes corresponding to the positions of the guide holes of the extraction liquid container, the guide holes of the quality control container, and the guide holes of the calibrator container, respectively. An upper limit layer is disposed between the guide layer and the lower limit layer, and the upper limit layer has upper limit holes corresponding to the positions of the guide holes of the extract container, the guide holes of the quality control container and the guide holes of the calibrator container respectively; A side wall receiving groove is provided on the side wall of the reagent rack facing the side wall of the box.
2. The reagent kit for detecting anticoagulant drug concentration in plasma as described in claim 1, characterized in that, The diameter of the guide hole in the extract container is larger than the diameter of the guide hole in the quality control container. The diameter of the guide hole in the quality control container is larger than that in the guide hole in the calibrator container.
3. The reagent kit for detecting anticoagulant drug concentration in plasma as described in claim 1, characterized in that, Labels are placed near the guide holes of the extraction liquid container, the quality control container, and the calibrator container.
4. The reagent kit for detecting anticoagulant drug concentration in plasma as described in claim 1, characterized in that, The lower limiting layer is made of sponge, and the diameter of the lower limiting hole is smaller than the diameter of its corresponding container.
5. The reagent kit for detecting anticoagulant drug concentration in plasma as described in claim 1, characterized in that, The upper limit layer is made of cardboard, the diameter of the upper limit hole is larger than the diameter of the corresponding container, and an elastic sheet extending from the hole wall to the center of the hole is formed circumferentially around the upper limit hole.
6. The reagent kit for detecting anticoagulant drug concentration in plasma as described in claim 1, characterized in that, The number of quality control containers is multiple, each used to hold blank quality control samples and quality control samples of different concentrations.
7. The reagent kit for detecting anticoagulant drug concentration in plasma as described in claim 1, characterized in that, The number of calibrator containers is multiple, each used to hold multiple calibrators of different concentrations.
8. The reagent kit for detecting anticoagulant drug concentration in plasma as described in claim 1, characterized in that, The box is equipped with a lid.