CN116859060A - Composite quality control product for inflammatory infection and preparation method and application thereof - Google Patents
Composite quality control product for inflammatory infection and preparation method and application thereof Download PDFInfo
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- CN116859060A CN116859060A CN202310739035.6A CN202310739035A CN116859060A CN 116859060 A CN116859060 A CN 116859060A CN 202310739035 A CN202310739035 A CN 202310739035A CN 116859060 A CN116859060 A CN 116859060A
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- quality control
- control product
- inflammatory
- level
- composite quality
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- 239000002131 composite material Substances 0.000 title claims abstract description 52
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- 230000002757 inflammatory effect Effects 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 239000011159 matrix material Substances 0.000 claims abstract description 44
- 210000002966 serum Anatomy 0.000 claims abstract description 38
- 206010061218 Inflammation Diseases 0.000 claims abstract description 34
- 230000004054 inflammatory process Effects 0.000 claims abstract description 34
- 241000282414 Homo sapiens Species 0.000 claims abstract description 32
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- CWCXERYKLSEGEZ-KDKHKZEGSA-N procalcitonin Chemical compound C([C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(O)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H]1NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@@H](N)CSSC1)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 CWCXERYKLSEGEZ-KDKHKZEGSA-N 0.000 claims abstract description 24
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- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 10
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- RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 claims description 6
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Classifications
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
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- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
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- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract
The invention discloses a composite quality control product for inflammatory infection, and a preparation method and application thereof, wherein the quality control product comprises matrix liquid and an inflammatory marker, wherein the matrix liquid contains human serum, a buffer, a protein protectant, a plasticizer, amino acid, sugar, a surfactant and a preservative, and the inflammatory marker comprises C-reactive protein, procalcitonin, serum amyloid A and interleukin-6; the quality control performance is stable, the device can be placed for 1 year at 2-8 ℃ in the dark, is suitable for joint detection of different inflammation projects, is convenient for clinical operation, saves cost, and provides guarantee for the accuracy of clinical test results.
Description
Technical Field
The invention belongs to the technical field of clinical detection, and particularly relates to a composite quality control product for inflammatory infection and a preparation method thereof, wherein the composite quality control product is suitable for clinical detection of inflammatory markers PCT, SAA, CRP and IL-6.
Background
Inflammation is a defensive reaction of an organism to external stimulus, is a clinically common disease and frequently encountered disease, and is mainly caused by invasion of bacteria, viruses and fungi into the body, and is mostly accompanied with fever. Infectious diseases caused by pathogens such as bacteria, viruses and fungi and products thereof are still one of the main causes of death and disability of human beings so far, and threaten the physical health of human beings. In clinic, the detection result of markers in the blood of a patient is usually used as the basis of evidence-based medical diagnosis, the accuracy of the measurement result of an inflammation detection and diagnosis system is not separated from the stable and qualified quality control, and whether the quality control product is in control is usually used for monitoring whether the whole laboratory detection system comprising detection instruments and reagents is effective or not in clinic, so that the accurate and reliable detection result of the patient is ensured.
Indoor quality control and daytime quality control are main links for ensuring the accuracy of a detection system, and the quality of the quality control product directly influences the accuracy of diagnosis. The quality control should have a high degree of compliance with the clinical sample, the ideal quality control should be free of matrix effects with the patient sample, uniform and stable, and should have less variability from vial to vial than the variation of the assay system, and contain one or more analytes at known concentrations. The quality control must be tested in the same manner as the patient sample.
The inflammation marker is a conventional detection project in clinical medicine laboratories at present, is a sensitive substance such as Procalcitonin (PCT), C-reactive protein (CRP), serum Amyloid A (SAA), interleukin-6 (IL-6) and the like, the content of which is increased due to the influence of infectious inflammatory factors when a stress reaction is generated after an organism is influenced by infection, wound or other diseases, is used as a protein of inflammatory reaction, has important auxiliary diagnostic significance in the early stage of infection and the inflammation development process, is not influenced by antibacterial drugs, immunosuppressants and hormones, and can be used as a reliable detection marker of an inflammatory infection composite quality control product. The detection significance of each item is different from that of clinical application, and the possibility of misdiagnosis exists when the infection degree is judged by only single marker content in clinical detection, so that the detection result is more fully and reliably by using the combined detection of multiple markers as the diagnosis basis. Most quality control products of inflammation detection items on the market are single quality control products, and the quality control products lack of composite commercialized quality control products, which means that the quality control detection needs to be repeated for a plurality of times by single mark substances in clinical medicine laboratories, and the operation is complex and complicated. Therefore, there is an urgent need in clinic for a composite quality control product with good commercialized stability for controlling the indoor quality and evaluating the indoor quality of clinical medicine laboratories.
Disclosure of Invention
In view of the above, the invention aims to provide a compound quality control product for inflammatory infection with stable performance, which has good accuracy and stability after a plurality of inflammatory markers are compounded, can be prepared into freeze-drying agent, has excellent reconstitution stability, and is greatly convenient for clinical medical laboratory use.
The technical scheme of the invention is as follows:
the composite quality control product for inflammatory infection comprises matrix liquid and an inflammation marker, wherein the matrix liquid consists of human serum and protective substances, and is prepared from the following components in detail:
the matrix liquid takes human serum as matrix and comprises 10-100 mM buffer, 10-30 g/L protein protectant, 1-50 g/L molding agent, 1-50 g/L amino acid, 1-50 g/L saccharide, 0.1-1 v/v% surfactant and 0.01-0.5 w/v% preservative;
markers of inflammation include C-reactive protein, procalcitonin, serum amyloid A and interleukin-6.
In the composite quality control product, the human serum is normal human serum, namely, the conventional detection results of HBsAg, HCV-Ab, HIV-Ab, TP and the like in the human serum are negative. The commercial human serum is used as the matrix, so that the matrix effect can be reduced to the greatest extent, the degree of coincidence with clinical samples is improved, and the human serum is a commercial product, has a stable purchasing channel, does not need centrifugal screening treatment, and is beneficial to quality control product production.
In the composite quality control product, the buffer can keep the pH of the matrix liquid stable, and reduce the influence of other additives on the pH. The buffer may be one or more of phosphate buffer, HEPES buffer, sodium citrate buffer, tris buffer, mops buffer, and the molar concentration is preferably 20-50 mM.
In the composite quality control product, the protein protecting agent is one or more of casein, casein hydrolysate, bovine serum albumin and gelatin.
In the composite quality control product, the amino acid is one or more of glycine, lysine and arginine, and the concentration of the amino acid in the matrix liquid is preferably 1-20 g/L.
In the composite quality control product, the saccharide is one or more of trehalose, sucrose, lactose and maltose, and the concentration of the saccharide in the matrix liquid is preferably 1-20 g/L.
In the composite quality control product, the molding agent is selected from one or more of mannitol, PEG, PVP and hydroxyethyl starch, and the concentration of the molding agent in the matrix liquid is preferably 1-20 g/L;
in the composite quality control product, the surfactant is one or more of polyethylene glycol 400, tween-20, trixon-100 and betaine, and the concentration of the surfactant in the matrix liquid is preferably 0.4-0.8 v/v%;
in the composite quality control product, the preservative is one or more of sodium azide, gentamicin sulfate and ProClin300.
As a preferable scheme, the composite quality control product for inflammatory infection provided by the invention specifically comprises matrix liquid and inflammatory markers, wherein:
the matrix liquid takes human serum as a matrix, has the pH of 4.5-5.5, and comprises 20-50 mM citric acid buffer, 10-30 g/L gelatin, 1-10 g/L mannitol, 1-10 g/L trehalose, 1-10 g/L glycine, 0.4-0.8% trixon-100, 0.2-1 g/L sodium azide, 0.2-1 g/L gentamicin sulfate and 0.02-0.1 w/v% Proclin300.
The markers of inflammation have two concentration levels, specifically: procalcitonin level is 1.4-0.6 ng/mL, and procalcitonin level is 2-24 ng/mL; the level of the C reaction protein is 1.8-1.2 mug/mL, and the level is 2-24 mug/mL; serum amyloid A level 1 4-6 mug/mL, level 2-24 mug/mL; interleukin-6 level 1-36 pg/mL, level 2-600 pg/mL.
In the preferred scheme, the method of compounding various preservatives can effectively remove the harm of various potential pathogenic microorganisms, so that the quality control product is safer to use.
More preferably, the matrix solution is human serum based, has a pH of 5.0, and comprises 50mM citric buffer, 20g/L gelatin, 5g/L mannitol, 5g/L trehalose, 5g/L glycine, 0.6% trixon-100, 0.9g/L sodium azide, 0.9g/L gentamicin sulfate, 0.05w/v% Proclin300. Experimental data show that the composite quality control product provided by the preferred scheme has high long-term stability and can be placed for 1 year at 2-8 ℃ in the dark.
The invention further provides a preparation method of the inflammation infection composite quality control product, which comprises the following steps:
the human serum is fully and uniformly mixed after being restored to room temperature, a certain amount of buffer is taken out, the buffer is added into the human serum, the pH is regulated after the human serum is fully and uniformly dissolved, the protein protectant, the shaping agent, the sugar, the amino acid and the preservative are added, the human serum is filtered after the human serum is completely dissolved, the volume is fixed by using the human serum, and the pH is regulated at the same time, so that matrix liquid is obtained; and adding the inflammation marker into the matrix liquid, testing the concentration level, and sub-packaging to obtain the composite quality control product.
In the above preparation method, filtration was performed using a 0.22 μm filter membrane.
In the preparation method, the test result of the concentration level of each inflammation marker is prepared in the concentration fluctuation range, and if the concentration is not in the range, a proper amount of corresponding antigen or matrix liquid can be taken and adjusted to be in the required range.
The composite quality control product for inflammatory infection can be prepared into freeze-dried powder after freeze-drying, and the freeze-dried powder is added with deionized water with the same volume for re-dissolution during split charging before use, and then is detected by a corresponding item detecting instrument to determine the target value and the quality control range of the quality control product. Experimental data show that the freeze-dried powder provided by the invention has good re-dissolution stability, can be stably stored for one week at 4 ℃ after re-dissolution, and has no obvious change trend in test results; and after one-time redissolution, the gel can be effectively stored for 2 months at the temperature of minus 20 ℃, so that the gel is greatly convenient for subsequent detection of users, and the detection cost is reduced.
The inflammation infection composite quality control product or the freeze-dried powder thereof provided by the invention can be used for detecting inflammation marker C reactive protein, procalcitonin, serum amyloid A and/or interleukin-6.
The beneficial effects of the invention are as follows:
1. the composite quality control product provided by the invention comprises a plurality of verification markers, so that quality control of a plurality of different detection items can be achieved by detecting one quality control sample, the joint detection of different inflammation items is realized, the operation flow is greatly simplified, and the composite quality control product has the advantages of low production cost, high accuracy and simplicity in operation.
2. The quality control product provided by the invention is used for simultaneously detecting a plurality of inflammation markers after being compounded, so that the interference is reduced, the difficulty of single quality control product item is solved, the quality control operation is simplified, and the clinical use is greatly facilitated.
3. The composite quality control product provided by the invention can be prepared into freeze-dried powder, multiple projects can be monitored at the same time by one freeze-drying, and the requirement of the re-dissolution stability at-20 ℃ in 60 days can be met, so that the production and use cost is greatly reduced.
4. The composite quality control product provided by the invention uses commercial human serum as matrix liquid, the channel source is stable, mass production can be realized, the clinical sample has high coincidence degree and strong universality, the matrix effect can be reduced to the greatest extent, the uniformity, the stability and other performances are good, and the detection accuracy is increased.
Detailed Description
For a better understanding of the present invention, the following will further illustrate the invention in connection with specific examples. It should be understood that the specific embodiments described herein are for purposes of illustration and explanation only and are not intended to limit the present invention.
Unless otherwise indicated, the examples were under routine experimental conditions or under conditions recommended by the manufacturer's instructions. The reagents and materials used, unless otherwise indicated, are commercially available.
Example 1
The embodiment provides a stable composite quality control product for inflammatory infection, which consists of matrix liquid and inflammatory markers, and comprises the following specific components:
the matrix liquid takes human serum as a matrix and comprises 50mM citric acid buffer, 20g/L gelatin, 5g/L mannitol, 5g/L trehalose, 5g/L glycine, 0.6v/v% trixon-100, 0.9g/L sodium azide, 0.9g/L gentamycin sulfate and 0.05w/v% Proclin300 (namely, 0.5g Proclin300 is contained in 1L matrix liquid).
The inflammation markers have two levels, namely a high level and a low level, and the content is specifically:
the low-level quality control product solution contains 0.4-0.6 ng/mL procalcitonin, 0.8-1.2 mug/mLC reaction protein, 4-6 mug/mL serum amyloid A and 24-36 pg/mL interleukin-6;
the high-level quality control product solution contains 16-24 ng/mL procalcitonin, 16-24 mug/mL C reaction protein, 16-24 mug/mL serum amyloid A and 400-600 pg/mL interleukin-6.
The composite quality control product is prepared into freeze-dried powder, and the specific steps are as follows:
(1) The human serum is fully and evenly mixed after being restored to room temperature, a certain amount of the serum is taken out, the citric acid buffer is added into the serum to ensure that the concentration of the serum reaches 50mM, and the pH is adjusted to 5.0 after the serum is fully dissolved and evenly mixed.
(2) 20g/L gelatin, 5g/L mannitol, 5g/L trehalose, 5g/L glycine, 0.6v/v% trixon-100, 0.9g/L sodium azide, 0.9g/L gentamycin sulfate, 0.05w/v% Proclin300 were added to the human serum after the pH adjustment in (1), and the human serum was fixed to a standard volume after complete dissolution, while the pH was adjusted again to 5.0.
(3) Filtering the prepared matrix liquid with a 0.22 μm filter membrane, taking out two parts, adding different amounts of inflammation markers, and mixing uniformly to obtain two levels of inflammation infection compound quality control products;
blending the content of the inflammation marker in the low-level quality control product to be: 0.4-0.6 ng/mL procalcitonin, 0.8-1.2 mug/mLC reaction protein, 4-6 mug/mL serum amyloid A, 24-36 pg/mL interleukin-6;
blending the content of the inflammation marker in the high-level quality control product to the following steps: 16-24 ng/mL procalcitonin, 16-24 mug/mL C reactive protein, 16-24 mug/mL serum amyloid A, 400-600 pg/mL interleukin-6.
The content is the content in the final freeze-dried product of the quality control product.
(4) And precisely subpackaging the prepared composite quality control product solution with high and low level concentrations into glass bottles, freezing and freeze-drying the semi-cover butyl rubber plug by a full-automatic vacuum freeze dryer, sealing the bottle by plugging in a vacuum state, taking out the bottle, covering a threaded plastic cover, and assigning values.
(5) Adding deionized water of the same volume for re-dissolution in split charging into the semi-finished product, and measuring and analyzing the content of each component in the quality control product by using a full-automatic chemiluminescence immunoassay analyzer (see table 1). And (5) after the quality control target value and the quality control range are determined to be qualified by inspection, labeling and packaging steps are carried out.
TABLE 1
Note that: the target values in the table are the average value of the measured values after freeze-drying and reconstitution, and the reference range is + -3 SD (quality control substance general-purpose grade requirement for in vitro diagnostic reagents- - - -YY/T1652-2019) of the average value of the measured values.
The results show that the two levels of the detection items contained in the inflammatory infection composite quality control product in this example are within the given range.
Performance verification was performed on the final finished quality control product prepared in example 1, including the following aspects:
1. and (5) testing uniformity.
The quality control product 10 bottles of example 1 of the same batch number are taken, the random number is 1-10, the test is carried out on a full-automatic chemiluminescence immunoassay analyzer with good precision, and each concentration level is repeatedly measured for 3 times. The 3 tests were performed in a different order, for example 1, 3, 5, 7, 9, 2, 4, 6, 8, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1,2, 4, 6, 8, 10, 1, 3, 5, 7, 9. Recording the detection result, and calculating F, sbb, sr and CV according to formulas 1-11 when the detection result has a numerical value Bottle room ；
Equation 1:
equation 2:
equation 3: SS (support System) In the bottle ＝SS Sum total -SS Bottle room ；
Equation 4:
equation 5:
equation 6:
equation 7: v 1 ＝a-1；
Equation 8: v 2 ＝N-a；
Equation 9:
equation 10:
equation 11:
wherein: SS-variance, x i Specifying the ith measurement or calculation of the parameter,total average value, n i Sample i number of repeated measurements, x ij The j-th result of sample i, MS-mean square, v-degree of freedom, F-F test value, n 0 Number of effective measurements, a number of samples extracted, N number of total tests, s bb Standard deviation between bottles, s r Standard deviation in bottle (repeatability standard deviation).
When F is less than or equal to 1, bysr replaces sbb to calculate CV between bottles, and CV should be calculated as a result Bottle room ≤10.0％；
When (when)When the test results show that the uniformity among bottles has no significant difference, the result should be CV Bottle room ≤10.0％；
When (when)The sbb was 0.3 delta or less, and it was considered that the uniformity between bottles was good, and CV was the result Bottle room ≤10.0％；
When (when)The sbb is more than 0.3 delta, and the uniformity among bottles is poor and is not satisfactory.
The uniformity test results are shown in tables 2 to 5:
TABLE 2
The results in table 2 show that both levels of the C-reactive protein (CRP) assay contained in the composite quality control of example 1 meet the uniformity requirement.
TABLE 3 Table 3
The results in Table 3 show that the composite quality control of example 1 meets the uniformity requirement at both levels of Serum Amyloid A (SAA) assay.
TABLE 4 Table 4
The results in Table 4 show that the composite quality control of example 1 meets the uniformity requirement at both levels for Procalcitonin (PCT) assay.
TABLE 5
The results in Table 5 show that the compound quality control of example 1 meets the uniformity requirement at both levels for interleukin-6 (IL-6) assay.
2. Acceleration stability test.
Taking 6 bottles of the quality control product of each level of example 1, wherein 3 sets of the bottles are placed in a refrigerator with the temperature of 2-8 ℃ for light-shielding refrigeration, and the other 3 bottles are placed in a constant temperature box with the temperature of 37 ℃. One bottle of samples was then tested on days 1, 4, and 7, respectively, while each node was tested with 1 bottle of chilled quality control as a control sample for each node. At the time of the test, 2 horizontal samples were repeatedly measured 2 times, and an average value was calculated. And calculating the relative deviation between the quality control measurement average value of each time node and the quality control measurement average value of the refrigeration control of each node, wherein the relative deviation is not more than +/-10%. The data are shown in Table 6.
TABLE 6
The results in table 6 show that the composite quality control of example 1 contained test items with both horizontal acceleration stability deviations of less than 10%.
3. And (3) testing the redissolution stability at the temperature of 2-8 ℃.
Taking 6 bottles of quality control products in each level of example 1, taking 3 sets of bottles as open bottle re-dissolution test samples, re-dissolving, placing the bottles in a refrigerator at 2-8 ℃ for light-proof refrigeration, and placing the other 3 sets of bottles in the refrigerator at 2-8 ℃ for light-proof preservation to serve as non-re-dissolution control samples. One set of the open-bottle reconstituted samples was taken at days 1, 4, and 7, respectively, while 1 set of non-reconstituted control samples were taken at each node for testing. At the time of testing, each quality control material concentration level sample was repeatedly measured 2 times, and an average value was calculated. The quality control product of the re-dissolution and the quality control product of the non-re-dissolution should be measured in the same operation, and the relative deviation of the measured average value of the quality control product at the end of the re-dissolution period and the measured average value of the non-re-solute control product is calculated.
TABLE 7
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The results in Table 7 show that the stability deviation of the two levels of the detection items contained in the composite quality control product in example 1 at 2-8 ℃ is less than 10%, which means that the quality control product has good redissolution stability.
4. The reconstitution stability at-20 ℃.
Taking 10 bottles of quality control products in each level of example 1, taking 5 sets of bottles as open bottle re-dissolution test samples, re-dissolving, placing the bottles in a refrigerator at the temperature of minus 20 ℃ for light-proof refrigeration, and placing the other 5 sets of bottles in a refrigerator at the temperature of 2-8 ℃ for light-proof preservation to serve as non-re-dissolution control samples. One open vial reconstituted sample was taken at days 10, 20, 30, 45, 60, respectively, while 1 additional set of non-reconstituted control samples was taken at each node for testing. At the time of testing, each quality control material concentration level sample was repeatedly measured 2 times, and an average value was calculated. The quality control product of the re-dissolution and the quality control product of the non-re-dissolution should be measured in the same operation, and the relative deviation of the measured average value of the quality control product at the end of the re-dissolution period and the measured average value of the non-re-solute control product is calculated.
TABLE 8
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The results in Table 8 show that the stability deviation of two levels of the detection items contained in the inflammation infection composite quality control product is less than 10 percent.
Example 2
The quality control product provided by the example consists of matrix liquid and inflammation markers, and comprises the following specific components:
the matrix liquid takes human serum as a matrix and comprises 50mM citric acid buffer, 20g/L gelatin, 5g/L mannitol, 5g/L trehalose, 5g/L glycine, 0.8v/v% trixon-100, 0.9g/L sodium azide, 0.9g/L gentamycin sulfate and 0.05w/v% Proclin300 (namely, 0.5g Proclin300 is contained in 1L matrix liquid).
The inflammation markers have two levels, namely a high level and a low level, and the content is specifically:
the low-level quality control product solution contains 0.4-0.6 ng/mL procalcitonin, 0.8-1.2 mug/mLC reaction protein, 4-6 mug/mL serum amyloid A and 24-36 pg/mL interleukin-6;
the high-level quality control product solution contains 16-24 ng/mL procalcitonin, 16-24 mug/mL C reaction protein, 16-24 mug/mL serum amyloid A and 400-600 pg/mL interleukin-6.
The composite quality control product is prepared into freeze-dried powder, and the specific steps are as follows:
(1) The human serum is fully and evenly mixed after being restored to room temperature, a certain amount of the serum is taken out, the citric acid buffer is added into the serum to ensure that the concentration of the serum reaches 50mM, and the pH is adjusted to 5.0 after the serum is fully dissolved and evenly mixed.
(2) 20g/L gelatin, 5g/L mannitol, 5g/L trehalose, 5g/L glycine, 0.8v/v% trixon-100, 0.9g/L sodium azide, 0.9g/L gentamycin sulfate, 0.05w/v% Proclin300 were added to the human serum after the pH adjustment in (1), and the human serum was fixed to a standard volume after complete dissolution, while the pH was adjusted again to 5.0.
(3) Filtering the prepared matrix liquid with a 0.22 μm filter membrane, taking out two parts, adding different amounts of inflammation markers, and mixing uniformly to obtain two levels of inflammation infection compound quality control products;
blending the content of the inflammation marker in the low-level quality control product to be: 0.4-0.6 ng/mL procalcitonin, 0.8-1.2 mug/mLC reaction protein, 4-6 mug/mL serum amyloid A, 24-36 pg/mL interleukin-6;
blending the content of the inflammation marker in the high-level quality control product to the following steps: 16-24 ng/mL procalcitonin, 16-24 mug/mL C reactive protein, 16-24 mug/mL serum amyloid A, 400-600 pg/mL interleukin-6.
The content is the content in the final freeze-dried product of the quality control product.
(4) And precisely subpackaging the prepared composite quality control product solution with high and low level concentrations into glass bottles, freezing and freeze-drying the semi-cover butyl rubber plug by a full-automatic vacuum freeze dryer, sealing the bottle by plugging in a vacuum state, taking out the bottle, covering a threaded plastic cover, and assigning values.
(5) Adding deionized water of the same volume for re-dissolution in split charging into the semi-finished product, and measuring and analyzing the content of each component in the quality control product by using a full-automatic chemiluminescence immunoassay analyzer (see table 9). And (5) after the quality control target value and the quality control range are determined to be qualified by inspection, labeling and packaging steps are carried out.
TABLE 9
The results show that the two levels of the detection items contained in the inflammatory infection composite quality control product in this example are within the given range.
Performance verification was performed on the final quality control product prepared in example 2:
1. acceleration stability test.
Taking 6 bottles of the quality control product of each level of example 1, wherein 3 sets of the bottles are placed in a refrigerator with the temperature of 2-8 ℃ for light-shielding refrigeration, and the other 3 bottles are placed in a constant temperature box with the temperature of 37 ℃. One bottle of samples was then tested on days 1, 4, and 7, respectively, while each node was tested with 1 bottle of chilled quality control as a control sample for each node. At the time of the test, 2 horizontal samples were repeatedly measured 2 times, and an average value was calculated. And calculating the relative deviation data of the quality control measurement average value of each time node and the quality control measurement average value of the refrigeration control of each node, wherein the relative deviation data is shown as 10.
Table 10
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Table 10 shows that when the content of trixon-100 in the composite quality control product of example 2 is increased to 0.8%, the relative deviation of the PCT item level 1 exceeds 10% in the test on the 7 th day, and the variation trend is obvious in the test process on the 7 th day; while there is no better directional optimization for other items, it can be seen that the performance of this example is inferior to the formulation of example 1.
In conclusion, the composite quality control product provided by the invention has good uniformity and stability, particularly the redissolution stability, can be stably stored for one week at 4 ℃ after redissolution, has no obvious change trend in test results, can be effectively stored for 2 months at-20 ℃ after one redissolution, and has important significance for clinical detection.
The embodiments described above are some, but not all embodiments of the invention. The detailed description of the embodiments of the invention is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Claims (10)
1. An inflammation infection composite quality control product is characterized by comprising a matrix fluid and an inflammation marker;
the matrix liquid takes human serum as a matrix and comprises 10-100 mM of buffering agent, 10-30 g/L of protein protecting agent, 1-50 g/L of molding agent, 1-50 g/L of amino acid, 1-50 g/L of saccharide, 0.1-1 v/v% of surfactant and 0.01-0.5 w/v% of preservative;
the inflammation markers include C-reactive protein, procalcitonin, serum amyloid A and interleukin-6.
2. The composite quality control for inflammatory infections according to claim 1, comprising a matrix fluid and an inflammatory marker;
the matrix liquid takes human serum as a matrix and comprises 20-50 mM of buffering agent, 10-30 g/L of protein protecting agent, 1-20 g/L of molding agent, 1-20 g/L of amino acid, 1-20 g/L of saccharide, 0.4-0.8 v/v% of surfactant and 0.01-0.5 w/v% of preservative;
the inflammation markers include C-reactive protein, procalcitonin, serum amyloid A and interleukin-6.
3. The composite quality control product for inflammatory infection according to claim 2, wherein the pH of the matrix solution is 4.5-6.0, and the buffer is one or more of phosphate buffer, HEPES buffer, sodium citrate buffer, tris buffer and Mops buffer;
the protein protecting agent is one or more of casein, casein hydrolysate, bovine serum albumin and gelatin;
the amino acid is one or more of glycine, lysine and arginine;
the saccharide is one or more of trehalose, sucrose, lactose and maltose;
the molding agent is one or more of mannitol, PEG, PVP and hydroxyethyl starch;
the surfactant is one or more of polyethylene glycol 400, tween-20 and trixon-100;
the preservative is one or more of sodium azide, gentamicin sulfate and ProClin300.
4. The composite quality control product for inflammatory infection according to claim 3, wherein the matrix liquid is based on human serum, has a pH of 4.5-5.5, and comprises 20-50 mM citric acid buffer, 10-30 g/L gelatin, 1-10 g/L mannitol, 1-10 g/L trehalose, 1-10 g/L glycine, 0.4-0.8% trixon-100, 0.2-1 g/L sodium azide, 0.2-1 g/L gentamicin sulfate, and 0.02% -0.1 w/v% Proclin300.
5. The composite quality control product for inflammatory infection according to claim 4, wherein the matrix liquid is based on human serum, has a pH of 5.0, and comprises 50mM citric acid buffer, 20g/L gelatin, 5g/L mannitol, 5g/L trehalose, 5g/L glycine, 0.6% trixon-100, 0.9g/L sodium azide, 0.9g/L gentamicin sulfate, and 0.05w/v% Proclin300.
6. The composite quality control for inflammatory infections according to claim 4, wherein the inflammatory markers each have two concentration levels, in particular: procalcitonin level is 1.4-0.6 ng/mL, and procalcitonin level is 2-24 ng/mL; the level of the C reaction protein is 10.8-1.2 mug/mL, and the level is 2-24 mug/mL; serum amyloid A level 1 4-6 mug/mL, level 2-24 mug/mL; interleukin-6 level 1-36 pg/mL, level 2-600 pg/mL.
7. The method for preparing the inflammatory infection composite quality control product according to any one of claims 1 to 6, which is characterized by comprising the following steps:
balancing human serum at room temperature, sequentially adding buffer, protein protectant, shaping agent, saccharide, amino acid and antiseptic, mixing, adjusting pH, and filtering to obtain matrix liquid; and adding the inflammation marker into the matrix liquid to obtain the composite quality control product.
8. The method of claim 7, wherein the filtration is performed with a 0.22 μm filter.
9. The freeze-dried powder of the composite quality control product for inflammatory infection, which is characterized by being obtained by freeze-drying the composite quality control product for inflammatory infection according to any one of claims 1 to 6.
10. Use of the inflammatory infection complex quality control product according to any one of claims 1 to 6 or the inflammatory infection complex quality control product freeze-dried powder according to claim 9 in detection of inflammatory markers C reactive protein, procalcitonin, serum amyloid a and/or interleukin-6.
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| CN202310739035.6A CN116859060A (en) | 2023-06-21 | 2023-06-21 | Composite quality control product for inflammatory infection and preparation method and application thereof |
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| CN202310739035.6A CN116859060A (en) | 2023-06-21 | 2023-06-21 | Composite quality control product for inflammatory infection and preparation method and application thereof |
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| CN (1) | CN116859060A (en) |
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