A stable calibrator and quality control

Abstract

This disclosure relates to stable calibrators and quality control materials. Specifically, it relates to the preparation and application of a pepsinogen calibrator and quality control material. The calibrator and quality control material provided in this disclosure includes: pepsinogen I, pepsinogen II, buffer solution, salt ions, amino acids, BSA, surfactant, and preservative. The calibrator and quality control material of this disclosure have improved stability to meet clinical requirements.

Description

Technical Field

[0001] This disclosure belongs to the field of in vitro diagnostic reagent technology, specifically relating to the preparation and application of a calibrator / quality control sample. Background Technology

[0002] Pepsinogen (PG) is a precursor of pepsin secreted by the stomach and involved in digestion. Usually, about 1% of PG can enter the bloodstream through the gastric mucosa. It can be divided into two subtypes, PGI and PGII. Serum pepsinogen can accurately reflect the state and function of the gastric mucosa.

[0003] As stomach diseases progress, serum PGI first rises and then falls, while PGII rises and then remains at a high level. Abnormalities in PGI, PGII, and the PGI / PGII ratio can indicate different stomach diseases. Therefore, PG is a preliminary screening indicator and a monitoring indicator for the treatment of stomach diseases such as superficial gastritis, erosive gastritis, gastric ulcer, duodenal ulcer, atrophic gastritis, and gastric cancer.

[0004] The general progression of some gastric cancers is as follows: Helicobacter pylori infection or other causes, gastritis, atrophic gastritis, intestinal metaplasia, dysplasia, and intestinal-type gastric cancer. If this process can be stopped as early as possible, the likelihood of developing gastric cancer is greatly reduced. This process is often accompanied by changes in progesterone (PG) levels. Reports indicate that one-third of patients diagnosed with gastric cancer had abnormal serum PG levels several years prior. Therefore, regular PG testing and active intervention are effective means of preventing gastric cancer.

[0005] In recent years, many studies have been conducted both domestically and internationally on the relationship between pepsinogen and various gastric diseases. Mukoubayashi et al. reported that PG can be used as a serum screening indicator for high-risk groups of precancerous lesions and gastric cancer. The Asia-Pacific consensus on gastric cancer prevention also points out that low serum PGI levels and low PGI / PGII ratios can be used as markers for screening high-risk groups of gastric cancer.

[0006] Latex immunoturbidimetric assay is a non-radioactive homogeneous immunoassay developed based on latex agglutination qualitative testing. It can accurately quantify various trace amounts of antigens and small molecule haptens. PG detection works by using specific antibodies-coated sensitized latex microparticles (typically polystyrene latex with a diameter of approximately 0.2 μm) to react with the corresponding PG antigen in the sample, resulting in agglutination and turbidity. The absorbance is measured, and the degree of turbidity is compared to the concentration of the analyte, showing a functional relationship. The generated dose-response curve allows for the determination of the PG antigen content in the sample.

[0007] There are existing calibrators for pepsinogen I and pepsinogen II detection kits based on latex immunoturbidimetry, used to calibrate and verify the accuracy of experimental results. Typically, calibrators for PGI and PGII are prepared separately, but this method is costly and prone to causing confusion in usage.

[0008] CN111024964A discloses a composite quality control product of pepsinogen I, pepsinogen II, and gastrin-17, comprising a protein preservation solution and pepsinogen I, pepsinogen II, and gastrin-17 dissolved in the protein preservation solution. The product contains 0.8-3.5 g / L of AEP-HBC, 0.002-0.006 g / L of fibrinogen, 0.05-0.15 g / L of gelatin, 2-8 g / L of trehalose, 0.05-0.25 g / L of tetrapolyphosphate, 5-25 mmol / L of 2-(N-morpholine)ethanesulfonic acid, 0.5-4 g / L of ethylenediaminetetraacetic acid or ethylenediaminetetraacetic acid salt, 1-20 mmol / L of cysteine, methionine, or arginine, and 0.05%-0.10% of preservatives. The composite quality control material disclosed in CN111024964A is stable for 14 months when stored at a temperature of 2-8℃.

[0009] Technicians are aware that pepsinogens can be classified into seven isoenzymes based on their migration rate under agarose gel electrophoresis, from fastest to slowest. Five of these are immunogenic and are called PGI; the other two have a slower migration rate and are called PGII. Therefore, the inventors noted that in existing technologies, it is difficult to ensure the stability of both pepsinogens when they are formulated into the same preparation. In view of this, there is still a need to provide a stable calibrator or quality control that can simultaneously ensure the activity and stability of both PGI and PGII. Summary of the Invention

[0010] This disclosure provides a highly stable calibrator and quality control for pepsinogen I / II detection. By precisely combining buffer solutions, salt ions, amino acids, protective agents, surfactants, and preservatives, and strictly controlling the pH of the system within the range of 7.0-7.5, it improves upon the problems of easy degradation and protein inactivation of traditional reagents, and can simultaneously ensure the activity and stability of PGI and PGII.

[0011] In some implementations, a stable calibrator is provided, which comprises or consists of the following: Pepsinogen I 0-600 ng / mL; Pepsinogen II 0-300 ng / mL; Buffer solution 10-100mM; Salt ions 50-200 mM; Amino acids 0.1-2 g / L; BSA 2.0-20g / L; Surfactant 0.1-1 g / L; Preservative 0.1-1g / L.

[0012] In some calibrator implementations, the buffer is selected from any of the following: phosphate buffer, HEPES buffer, glycine buffer, Tris-HCl buffer, MOPS buffer, and MES buffer.

[0013] In some embodiments of the calibrator, the pH of the calibrator is not more than 7.5 and not less than 7.0.

[0014] In some embodiments of the calibrator, the salt ion is selected from any one of the following: sodium chloride, potassium chloride, magnesium chloride, and sodium carbonate.

[0015] In some embodiments of the calibrator, the amino acid is selected from any of the following: glycine, alanine, leucine, tyrosine, and glutamic acid.

[0016] In some embodiments of the calibrators, the surfactant is selected from any of the following: Tween-20, Tween-80, AEO-3, AEO-7.

[0017] In some calibrator implementations, the surfactant is not selected from any of the following: Brij-L23, S9, Triton-100.

[0018] In some embodiments of the calibrators, the preservative is selected from any of the following: sodium azide, thimerosal, PC300.

[0019] In some embodiments of the calibrator, the calibrator does not contain any one or a combination of the following: AEP-HBC, fibrinogen, gelatin, trehalose, tetrapolyphosphate, cysteine, methionine, and arginine.

[0020] In one specific implementation, the stable calibrator comprises or consists of the following: Pepsinogen I is available at levels 1: 0 ng / mL, 2: 20 ng / mL, 3: 70 ng / mL, 4: 135 ng / mL, 5: 190 ng / mL, and 6: 250 ng / mL. Pepsinogen II is available at levels 1: 0 ng / mL, 2: 5 ng / mL, 3: 15 ng / mL, 4: 30 ng / mL, 5: 60 ng / mL, and 6: 100 ng / mL. Phosphate buffer 50mM; 100mM sodium chloride; Glycine 0.5 g / L; BSA 5g / L; Tween-20 0.2 g / L; Preservative 1g / L; pH 7.0.

[0021] In one specific implementation, the stable calibrator comprises or consists of the following: Pepsinogen I is available at levels 1: 0 ng / mL, 2: 20 ng / mL, 3: 70 ng / mL, 4: 135 ng / mL, 5: 190 ng / mL, and 6: 250 ng / mL. Pepsinogen II is available at levels 1: 0 ng / mL, 2: 5 ng / mL, 3: 15 ng / mL, 4: 30 ng / mL, 5: 60 ng / mL, and 6: 100 ng / mL. HEPES buffer 100mM; Potassium chloride 200mM; Tyrosine 1 g / L; BSA 2g / L; Tween-80 0.1 g / L; Preservative 1g / L; pH 7.5.

[0022] In some implementations, a stable quality control sample is also provided, which comprises or consists of the following: Pepsinogen I is available at levels 1: 35 ng / mL and 2: 75 ng / mL; Pepsinogen II is available at levels 1: 10 ng / mL and 2: 40 ng / mL; Buffer solution 10-100mM; Salt ions 50-200 mM; Amino acids 0.1-2 g / L; BSA 2.0-20g / L; Surfactant 0.1-1 g / L; Preservative 0.1-1g / L.

[0023] In some implementations of quality control products, the buffer solution is selected from any of the following: phosphate buffer, HEPES buffer, glycine buffer, Tris-HCl buffer, MOPS buffer, and MES buffer.

[0024] In some implementations of quality control products, the pH of the calibrator is not more than 7.5 and not less than 7.0.

[0025] In some implementation schemes for quality control products, the salt ions are selected from any one of the following: sodium chloride, potassium chloride, magnesium chloride, and sodium carbonate.

[0026] In some implementation schemes of quality control products, the amino acid is selected from any one of the following: glycine, alanine, leucine, tyrosine, and glutamic acid.

[0027] In some implementations of quality control products, the surfactant is selected from any of the following: Tween-20, Tween-80, AEO-3, and AEO-7.

[0028] In some implementations of quality control products, the surfactant is not selected from any of the following: Brij-L23, S9, Triton-100.

[0029] In some implementation schemes for quality control products, the preservative is selected from any one of the following: sodium azide, thimerosal, and PC300.

[0030] In some implementations of quality control products, the calibrator does not contain any one or a combination of the following: AEP-HBC, fibrinogen, gelatin, trehalose, tetrapolyphosphate, cysteine, methionine, and arginine.

[0031] In one specific implementation, the stable quality control material comprises or consists of the following: Pepsinogen I is available at levels 1: 35 ng / mL and 2: 75 ng / mL; Pepsinogen II is available at levels 1: 10 ng / mL and 2: 40 ng / mL; Phosphate buffer 50mM; 100mM sodium chloride; Glycine 0.5 g / L; BSA 5g / L; Tween-20 0.2 g / L; Preservative 1g / L; pH 7.0.

[0032] In one specific implementation, the stable quality control material comprises or consists of the following: Pepsinogen I is available at levels 1: 35 ng / mL and 2: 75 ng / mL; Pepsinogen II is available at levels 1: 10 ng / mL and 2: 40 ng / mL; HEPES buffer 100mM; Potassium chloride 200mM; Tyrosine 1 g / L; BSA 2g / L; Tween-80 0.1 g / L; Preservative 1g / L; pH 7.5.

[0033] This disclosure also provides the use of any of the aforementioned stable calibrators in the preparation of pepsinogen detection kits. The calibrators can be used as graded calibration reagents for the kit, packaged together with the antibody reagents, buffer solutions, reaction solutions, and other components in the kit, and are suitable for mainstream PGI / PGII quantitative detection platforms such as latex immunoturbidimetry, chemiluminescent immunoassay, enzyme-linked immunosorbent assay (ELISA), and fluorescence immunoassay.

[0034] This disclosure also provides the use of any of the aforementioned stable quality control materials in the preparation of a pepsinogen detection kit. The quality control material is available in two concentration levels, low and high, and can also be used in conjunction with gradient calibrators to form a complete calibration and quality control system for the kit. Detailed Implementation

[0035] Part 1. Calibrators Example 1A. Calibrator of this application Pepsinogen I is available at levels 1: 0 ng / mL, 2: 20 ng / mL, 3: 70 ng / mL, 4: 135 ng / mL, 5: 190 ng / mL, and 6: 250 ng / mL. Pepsinogen II is available at levels 1: 0 ng / mL, 2: 5 ng / mL, 3: 15 ng / mL, 4: 30 ng / mL, 5: 60 ng / mL, and 6: 100 ng / mL. Phosphate buffer 50mM Sodium chloride 100mM Glycine 0.5 g / L BSA 5g / L Tween-20 0.2g / L Preservative 1g / L pH 7.0; The buffer solution, salt, amino acid, BSA, surfactant, and preservative were dissolved in purified water and then thoroughly mixed to form a matrix solution. The pH of the solution was adjusted to the target pH. The matrix solution was filtered using a 0.45 μm filter membrane. The amounts of PGI and PGII were calculated according to the calibrator concentration requirements, added to the matrix solution, and thoroughly mixed to obtain the liquid calibrator.

[0036] Example 2A. Calibrator of this application Pepsinogen I is available at levels 1: 0 ng / mL, 2: 20 ng / mL, 3: 70 ng / mL, 4: 135 ng / mL, 5: 190 ng / mL, and 6: 250 ng / mL. Pepsinogen II is available at levels 1: 0 ng / mL, 2: 5 ng / mL, 3: 15 ng / mL, 4: 30 ng / mL, 5: 60 ng / mL, and 6: 100 ng / mL. HEPES buffer 100mM Potassium chloride 200mM Tyrosine 1g / L BSA 2g / L Tween-80 0.1g / L Preservative 1g / L pH 7.5.

[0037] The preparation steps are the same as in Example 1A.

[0038] Comparative Example 1A. Comparative Calibrator 1 (with surfactant replacement) The difference from Example 1A is that the surfactant is replaced with 0.2 g / L Brij-L23.

[0039] Control Example 2A: Control Calibrator 2 (replaces pH 8.0) The difference from Example 1A is that the pH is replaced with 8.0.

[0040] Reference Example 3A: Reference Calibrator 3 The difference from Example 2A is that the pH is replaced with 6.5 (the buffer environment taught in prior art CN111024964A).

[0041] Comparative Example 4A. Protectant / Stabilizer Fibrinogen and gelatin are common protective agents or stabilizers in the art. The applicant unexpectedly found that replacing BSA in the calibrators of Examples 1A and 2A with fibrinogen or gelatin could also improve accelerated stability and shelf stability, but the performance in transport stability and freeze-thaw stability was not ideal. Irreversible precipitation could be observed, and the trend became more obvious with the increase of freeze-thaw cycles.

[0042] Test Example 1. Accelerated Stability The accelerated stability at 37°C of the calibrators prepared in Examples 1A and 2A, and the control calibrator, was tested. The results are shown in Table 1.

[0043] Table 1. Accelerated stability at 37°C Examples 1A and 2A showed good stability, with no statistically significant difference in measured values ​​after acceleration at 37°C. Control Examples 1A, 2A, and 3A all showed a decreasing trend in stability measured at 37°C, with some concentrations decreasing by more than 10%.

[0044] Test Example 2. Resistance to Mechanical Shear Force The transport stability of the calibrators and control calibrators prepared in Examples 1A and 2A was tested.

[0045] Transportation stability test method: Transportation limit condition test. Under normal temperature conditions, reagents were transported to Shanghai, then transferred to Guangzhou, and finally transported back to the origin. The same batch of reagents was used to simultaneously test both transported and untransported calibrators three times each, and the average value was calculated. The percentage change was calculated, and a percentage change of less than 10% was acceptable. The results are shown in Table 2.

[0046] Table 2. Transportation Stability Both Example 1A and Example 2A showed good transport stability, while individual measurements of Control Examples 1A to 3A showed changes after transport.

[0047] Test Example 3. Shelf Stability The shelf stability of the calibrators prepared in Examples 1A and 2A, and the control calibrators, was tested. The results are shown in Tables 3 and 4.

[0048] Table 3. Shelf stability at 4°C and -20°C Conclusion: There was no statistically significant difference in the measured values ​​of Examples 1A and 2A when stored at -20℃, while the measured values ​​of Control Examples 1A to 3A decreased.

[0049] Table 4. Shelf stability at -80°C The measured values ​​of Examples 1A and 2A showed relatively small changes when stored at -80℃, and the results were better than those of Control Examples 1A to 3A.

[0050] Test Example 4. Freeze-thaw stability The freeze-thaw stability of the calibrators prepared in Example 1A and Example 2A and the control calibrator were tested.

[0051] Experimental procedure: Calibrators were placed at -20℃ for at least 24 hours, then removed and allowed to thaw naturally at room temperature; this process was considered one freeze-thaw cycle. Calibrators that had undergone one freeze-thaw cycle were placed at -20℃ for at least 24 hours, then removed and allowed to thaw naturally at room temperature; this process was considered two freeze-thaw cycles. Calibrators that had undergone two freeze-thaw cycles were placed at -20℃ for at least 24 hours, then removed and allowed to thaw naturally at room temperature; this process was considered three freeze-thaw cycles. The effect of repeated freeze-thaw cycles on the measured values ​​of the calibrators was investigated. The results are shown in Tables 5 to 7.

[0052] Table 5. Freeze-thaw stability (1 freeze-thaw cycle) Table 6. Freeze-thaw stability (2 freeze-thaw cycles) Table 7. Freeze-thaw stability (3 freeze-thaw cycles) The values ​​of the calibrators in Examples 1A and 2A did not change significantly after three freeze-thaw cycles, while the values ​​of some calibrators in Control Examples 1A, 2A, and 3A decreased after three freeze-thaw cycles.

[0053] Part Two. Quality Control Products Example 1B. Quality control sample of this application Pepsinogen I is available at levels 1: 35 ng / mL and 2: 75 ng / mL; Pepsinogen II is available at levels 1: 10 ng / mL and 2: 40 ng / mL; Phosphate buffer 50mM Sodium chloride 100mM Glycine 0.5 g / L BSA 5g / L Tween-20 0.2g / L Preservative 1g / L pH 7.0.

[0054] Example 2B. Quality control sample of this application Pepsinogen I is available at levels 1: 35 ng / mL and 2: 75 ng / mL; Pepsinogen II is available at levels 1: 10 ng / mL and 2: 40 ng / mL; HEPES buffer 100mM Potassium chloride 200mM Tyrosine 1g / L BSA 2g / L Tween-80 0.1g / L Preservative 1g / L pH 7.5.

[0055] The preparation steps are the same as in Example 1B.

[0056] Comparative Example 1B. Control Sample 1 (with a replacement surfactant) The difference from Example 1B is that the surfactant is replaced with 0.2 g / L Brij-L23.

[0057] Control Example 2B. Control Sample 2 (pH Replacement) The difference from Example 1B is that the pH is replaced with 8.0.

[0058] Compare with Example 3B. Compare with quality control sample 3. The difference from Example 2B is that the pH is replaced with 6.5 (the buffer environment taught in CN111024964A).

[0059] Comparative Example 4B. Protectant / Stabilizer Fibrinogen and gelatin are common protective agents or stabilizers in the art. The applicant unexpectedly found that replacing BSA in the quality control samples of Examples 1B and 2B with fibrinogen or gelatin could also improve accelerated stability and shelf stability, but the performance in transport stability and freeze-thaw stability was not ideal. Irreversible precipitation could be observed, and the trend of decreased stability became more obvious with the increase of freeze-thaw cycles.

[0060] Test Example 5. Accelerated Stability The accelerated stability at 37°C was tested for the quality control samples prepared in Examples 1B and 2B, as well as the control sample. The results are shown in Table 8.

[0061] Table 8. Accelerated stability at 37°C Examples 1B and 2B showed good stability, with no statistically significant difference in measured values ​​after acceleration at 37°C. However, the measured values ​​after acceleration at 37°C varied from Control Examples 1B to Control Examples 3B, with deviations exceeding 10%.

[0062] Test Example 6: Resistance to Mechanical Shear Force The transport stability of the quality control samples and control samples prepared in Examples 1B and 2B was tested. Transport stability test method: Under extreme transport conditions, the reagents were transported to Shanghai, then transferred to Guangzhou, and finally returned to the origin. The transported and untransported quality control samples were tested simultaneously three times each using the same batch of reagents, and the average value was calculated. The percentage change was calculated; a percentage change of less than 10% was acceptable.

[0063] The results are shown in Table 9.

[0064] Table 9. Transportation Stability Both Example 1B and Example 2B showed good transport stability, while the measured values ​​of Control Examples 1B to 3B changed after transport.

[0065] Test Example 7. Shelf Stability The shelf stability of the quality control samples and control samples prepared in Examples 1B and 2B was tested. The results are shown in Tables 10 and 11.

[0066] Table 10. Shelf stability at 4°C and -20°C Table 11. Shelf stability at -80°C Test Example 8. Freeze-thaw stability The freeze-thaw stability of the quality control samples and control samples prepared in Examples 1B and 2B was tested.

[0067] Experimental procedure: Quality control samples were placed at -20℃ for at least 24 hours, then removed and allowed to thaw naturally at room temperature. This process was repeated once. Quality control samples that had undergone one freeze-thaw cycle were placed at -20℃ for at least 24 hours, then removed and allowed to thaw naturally at room temperature. This process was repeated twice. Quality control samples that had undergone two freeze-thaw cycles were placed at -20℃ for at least 24 hours, then removed and allowed to thaw naturally at room temperature. This process was repeated three times. The effect of repeated freeze-thaw cycles on the measured values ​​of the quality control samples was investigated.

[0068] Table 12. Freeze-thaw stability Table 13. Freeze-thaw stability / 2 freeze-thaw cycles Table 14. Freeze-thaw stability / 3 freeze-thaw cycles The values ​​of the quality control samples in Examples 1B and 2B did not change significantly after three freeze-thaw cycles, while the values ​​of some control samples in Control Examples 1B to 3B decreased after three freeze-thaw cycles.

Claims

1. A stable calibrator comprising or consisting of the following: Pepsinogen I 0-600 ng / mL; Pepsinogen II 0-300 ng / mL; Buffer solution 10-100mM; Salt ions 50-200 mM; Amino acids 0.1-2 g / L; BSA 2.0-20g / L; Surfactant 0.1-1 g / L; Preservative 0.1-1g / L; The buffer solution is selected from any of the following: phosphate buffer, HEPES buffer, glycine buffer, Tris-HCl buffer, MOPS buffer, MES buffer; The pH of the calibrator is not more than 7.5 and not less than 7.0; The salt ion is selected from any one of the following: sodium chloride, potassium chloride, magnesium chloride, sodium carbonate; The amino acid is selected from any one of the following: glycine, alanine, leucine, tyrosine, and glutamic acid; The surfactant is selected from any one of the following: Tween-20, Tween-80, AEO-3, AEO-7; The surfactant is not selected from any of the following: Brij-L23, S9, Triton-100; The preservative is selected from any one of the following: sodium azide, thimerosal, PC300; Preferably, the calibrator does not contain any one or a combination of the following: AEP-HBC, fibrinogen, gelatin, trehalose, tetrapolyphosphate, cysteine, methionine, and arginine.

2. The stable calibrator according to claim 1, comprising or consisting of the following: Pepsinogen I is available at levels 1: 0 ng / mL, 2: 20 ng / mL, 3: 70 ng / mL, 4: 135 ng / mL, 5: 190 ng / mL, and 6: 250 ng / mL. Pepsinogen II is available at levels 1: 0 ng / mL, 2: 5 ng / mL, 3: 15 ng / mL, 4: 30 ng / mL, 5: 60 ng / mL, and 6: 100 ng / mL. Phosphate buffer 50mM; 100mM sodium chloride; Glycine 0.5 g / L; BSA 5g / L; Tween-20 0.2 g / L; Preservative 1g / L; pH 7.

0.

3. The stable calibrator according to claim 1, comprising or consisting of the following: Pepsinogen I is available at levels 1: 0 ng / mL, 2: 20 ng / mL, 3: 70 ng / mL, 4: 135 ng / mL, 5: 190 ng / mL, and 6: 250 ng / mL. Pepsinogen II is available at levels 1: 0 ng / mL, 2: 5 ng / mL, 3: 15 ng / mL, 4: 30 ng / mL, 5: 60 ng / mL, and 6: 100 ng / mL. HEPES buffer 100mM; Potassium chloride 200mM; Tyrosine 1 g / L; BSA 2g / L; Tween-80 0.1 g / L; Preservative 1g / L; pH 7.

5.

4. A stable quality control product, comprising or consisting of the following: Pepsinogen I is available at levels 1: 35 ng / mL and 2: 75 ng / mL; Pepsinogen II is available at levels 1: 10 ng / mL and 2: 40 ng / mL; Buffer solution 10-100mM; Salt ions 50-200 mM; Amino acids 0.1-2 g / L; BSA 2.0-20g / L; Surfactant 0.1-1 g / L; Preservative 0.1-1g / L; The buffer solution is selected from any of the following: phosphate buffer, HEPES buffer, glycine buffer, Tris-HCl buffer, MOPS buffer, MES buffer; The pH of the quality control sample is not more than 7.5 and not less than 7.0; The salt ion is selected from any one of the following: sodium chloride, potassium chloride, magnesium chloride, sodium carbonate; The amino acid is selected from any one of the following: glycine, alanine, leucine, tyrosine, and glutamic acid; The surfactant is selected from any one of the following: Tween-20, Tween-80, AEO-3, AEO-7; The surfactant is not selected from any of the following: Brij-L23, S9, Triton-100; The preservative is selected from any one of the following: sodium azide, thimerosal, PC300; Preferably, the quality control product does not contain any one or a combination of the following: AEP-HBC, fibrinogen, gelatin, trehalose, tetrapolyphosphate, cysteine, methionine, and arginine.

5. The stable quality control product according to claim 4, comprising or consisting of the following: Pepsinogen I is available at levels 1: 35 ng / mL and 2: 75 ng / mL; Pepsinogen II is available at levels 1: 10 ng / mL and 2: 40 ng / mL; Phosphate buffer 50mM; 100mM sodium chloride; Glycine 0.5 g / L; BSA 5g / L; Tween-20 0.2 g / L; Preservative 1g / L; pH 7.

0.

6. The stable quality control product according to claim 4, comprising or consisting of the following: Pepsinogen I is available at levels 1: 35 ng / mL and 2: 75 ng / mL; Pepsinogen II is available at levels 1: 10 ng / mL and 2: 40 ng / mL; HEPES buffer 100mM; Potassium chloride 200mM; Tyrosine 1 g / L; BSA 2g / L; Tween-80 0.1 g / L; Preservative 1g / L; pH 7.

5.

7. Use of the stable calibrator according to any one of claims 1 to 3 in the preparation of a pepsinogen detection kit.

8. Use of the stable quality control product according to any one of claims 4 to 6 in the preparation of a pepsinogen detection kit.

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