Some standard content:
ICS07.080
National Standard of the People's Republic of China
GB/T38171—2019
Metal chelating chromatographic medium
Metal chelating chromatographic medium2019-10-18Issued
State Administration for Market Regulation
Standardization Administration of the People's Republic of China
2019-10-18Implemented
This standard was drafted in accordance with the rules given in GB/T1.1-2009. This standard was proposed and managed by the China National Institute of Standardization. GB/T38171—2019
Drafting units of this standard: Institute of Process Engineering, Chinese Academy of Sciences, China National Institute of Standardization, and Zhongke Senhui Microsphere Technology (Suzhou) Co., Ltd.
The main drafters of this standard are Huang Yongdong, Zhao Lan, Zhu Kai, Wu Xuexing, Ma Guanghui, Su Zhiguo, Gong Fangling, Ma Aijin, Yang Weixing and Wang Shaoyun. 1
1Scope
Metal chelate chromatography media
GB/T38171—2019
This standard specifies the classification, technical requirements, test methods, inspection rules, labeling, marking, packaging, transportation and storage of metal chelate chromatography media.
This standard applies to the production and testing of metal chelate chromatography media. Normative reference documents
The following documents are indispensable for the application of this document. For all dated reference documents, only the dated version applies to this document. For all undated reference documents, the latest version (including all amendments) applies to this document. GB/T191
Packaging, storage and transportation pictorial marking
Ion exchange resin sampling method
GB/T5475
GB/T6682
Specifications and test methods for water used in analytical laboratories Pharmacopoeia of the People's Republic of China (2015 edition) 3
Terms and definitions
The following terms and definitions apply to this document. Metal chelating chromatographic medium
metal chelatingchromatographicmedium A type of chromatographic medium formed by bonding iminodiacetic acid or nitrilotriacetic acid to an agarose separation medium and then chelating the metal ion Ni2+ (or other metal ions). 4 Classification
According to the type of chelating agent, it is divided into iminodiacetic acid type metal chelating chromatographic medium (IDA) and nitrilotriacetic acid type metal chelating chromatographic medium (NTA).
Technical requirements
Appearance requirements
Metal chelate chromatography media should be spherical and full, with a smooth surface, and should be transparent under an optical microscope. 5.2
Performance requirements
Should comply with the requirements in Table 1.
GB/T 38171—2019
Main performance requirements of metal chelate chromatography media
Range Particle size ratio (W)/%
Average particle size (a)/μm
Maximum flow rate/(cm/h)
Ligand density/(μmol/mL)
Dynamic binding capacity (Qso%)d/(mg/mL)
Total colony count/(CFU/mL)
5-hydroxymethylfurfural shedding amount/(μg/mL)pH3.0
90.0±13.5
The ratio of the volume of sample particles with a particle size of 45.0μm165.0μm to the volume of all sample particles. The maximum flow rate can be achieved at a pressure of 0.10MPa. b
The amount of Ni+ chelated per milliliter of medium.
The amount of lactate dehydrogenase (His-tagged LDH) adsorbed per milliliter of medium. 6 Detection method
6.1 Appearance
Sample treatment
According to GB/T5475, 5 mL of sample is directly extracted from the product and placed in a 50 mL G3 sand core funnel and drained for 5 minutes. Wash with grade tertiary water that complies with GB/T6682 for 5 times, 2 minutes each time, and finally use a vacuum pump to drain for 5 minutes at a pressure of 0.1 MPa. Place the washed metal chelate chromatography medium in a beaker and add grade tertiary water to it to ensure that there should be 2 cm of grade tertiary water on the metal chelate chromatography medium. After mixing, a mixed system of metal chelate chromatography medium and water is obtained. 6.1.2 Sample observationbZxz.net
Use a plastic pipette to absorb the mixed system and place it on a slide, and adjust the microscope magnification. Taking the metal chelate chromatography medium as the standard when more than 80% of the area in the field of view is metal chelate chromatography medium, use a plastic pipette to increase or decrease the metal chelate chromatography medium on the slide, and finally press it with a cover glass. Adjust the focal length of the optical microscope to make the image in the field of view clear. Take a photo of the metal chelate chromatography medium and save it. 2 Particle size
Sample processing
The method is the same as 6.1.1.
Sample detection
Set the laser particle size analyzer parameters as follows: the measurement particle type is universal type, the dispersant type is water, the analysis mode is single peak mode, and the sample is added for measurement.
6.2.3 Result calculation
Range particle size ratio
Calculate according to formula (1):
W teaching diameter
W teaching control
Range particle size ratio, %;
The ratio of the volume of particles with a particle size of k (um) to the volume of all sample particles, %. The average particle size
is calculated according to formula (2):
wherein:
the average particle size of a certain number of medium particles counted, in micrometers (μum); the particle size of a single particle, in micrometers (um); N—the number of medium particles counted.
GB/T38171—2019
(1)
(2)
The absolute difference between three independent determination results obtained under repeatability conditions shall not exceed 10% of the arithmetic mean. 6.3 Maximum flow rate
Sample treatment
The method is the same as 6.1.1.
6.3.2 Sample column loading
Select a chromatography column with a size of ?1.60cm×20.00cm, block the column outlet, pour the mixed slurry of medium and water into the chromatography column, and let it stand. Control the medium bed height to 10.00cm ± 0.20cm, and fill the top of the column with water. Open the column inlet and continuously introduce 10 column volumes of tertiary water into the column at a flow rate of 0.5mL/min. The test can be carried out after the bed is stable. 6.3.3 Sample determination
Connect the chromatography column to the medium and low pressure chromatography system. When measuring, set a certain flow rate u (mL/min) from zero, maintain the flow rate for 5 minutes, and record the column pressure p (MPa) at this time. Continue to increase the flow rate and measure the column pressure at the corresponding flow rate. Until the pressure reaches 0.10MPa, the corresponding flow rate is recorded as Uo.1. 6.3.4 Result calculation
Calculate according to formula (3):
Maximum flow rate, in centimeters per hour (cm/h); Volume flow rate at 0.10MPa pressure, in milliliters per minute (mL/min); (3)
GB/T38171—2019
Cross-sectional area of a column, in square centimeters (cm): 60
Conversion factor from minutes to hours.
The absolute difference between the three independent determination results obtained under repeatability conditions shall not exceed 10% of the arithmetic mean. 6.4 Ligand density
6.4.1 Solution preparation
Ammonia-ammonium chloride buffer A, pH 10.0
Dissolve 68.00 g of ammonium chloride in 300 mL of grade 3 water, add 570 mL of concentrated ammonia water, dilute with grade 3 water, adjust the pH to 10.0, and finally make up to 1000 mL.
6.4.1.2 Ammonia-ammonium chloride buffer B·pH 10.0 Weigh 5.40 g of ammonium chloride, add 50 mL of grade 3 water to dissolve, add 35 mL of concentrated ammonia water, dilute with grade 3 water, adjust the pH to 10.0, and finally make up to 100 mL.
6.4.1.35 g/L Eriochrome Black T indicator solution
Weigh 0.50 g of Eriochrome Black T, add 4.00 g of hydroxylamine hydrochloride and dissolve in 100 mL of ethanol. 6.4.1.4 Murexamide indicator
Weigh 1.00g of Murexamide, add 100.00g of sodium chloride and grind into powder in a mortar, put into a clean brown wide-mouth bottle for later use. 6.4.1.5 0.10mol/L disodium ethylenediaminetetraacetate (abbreviated as EDTA standard solution) Weigh 40.00g disodium ethylenediaminetetraacetate, dissolve in 1000mL of grade 3 water, cool and shake well. 6.4.1.6 0.10mol/L calibration of EDTA standard solution Weigh 0.2500g of reference zinc oxide burned to constant weight at 800C, weigh to 0.0001g. Moisten with a small amount of grade 3 water, add 5mL of 20% hydrochloric acid solution to dissolve the sample.Add 10mL of grade 3 water, neutralize with 10% ammonia solution to pH 7-8, add 10mL of ammonia-ammonium chloride buffer A (pH 10) and 5 drops of 5g/L chrome black T indicator solution, and titrate with the prepared EDTA standard solution until the solution changes from purple to pure blue. Perform a blank test at the same time.
6.4.1.7 Calculation of EDTA standard solution concentration
Calculate according to formula (4):
CEDTA=(V/-V)×0.08138
Wherein:
Concentration of disodium ethylenetriaminetetraacetic acid standard solution, in moles per liter (mol/L): mass of zinc oxide, in grams (g); amount of disodium ethylenediaminetetraacetic acid solution, in milliliters (mL); amount of disodium ethylenediaminetetraacetic acid used in blank test, in milliliters (mL); 0.08138——Conversion factor for converting 1.00mL disodium ethylenediaminetetraacetic acid standard solution into equivalent mass of zinc oxide. 6.4.1.80.05mol/LNi(NO3)2 standard solution Weigh 1.45gNi(NO,)2·6H,O and dissolve it in 100mL of grade tertiary water. 4
（4）
6.4.1.9 Calibration of 0.05mol/L Ni(NO3)2 standard solution GB/T38171—2019
Accurately measure 50mL of the above-prepared Ni(NO3)2 solution and place it in a 250mL conical flask, adjust the pH value to 7~8 with ammonia water, add 50mL of ammonia-ammonium chloride buffer B, 0.25g of murexamide indicator, and titrate with 0.1mol/L EDTA standard solution until the solution changes from yellow to purple. Record the volume of EDTA standard solution consumed VeDTA.a. 6.4.2 Sample treatment
According to GB/T5475, directly extract 5mL of sample from the product and place it in a 50mL G3 sand core funnel. Wash with grade tertiary water for 5 times, 2 minutes each time, and then wash with 0.1mol/LEDTA solution for 5 times, 5 minutes each time, to clean the chelated metal ions on the medium, and finally wash with grade tertiary water for 5 times, 2 minutes each time, and vacuum pump for 5 minutes at a pressure of 0.1MPa. 6.4.3 Sample column loading
Weigh 2.00g of the dried medium, pour the mixed slurry with water into the chromatography column, block the column outlet, and let it stand until the column bed is stable. Open the column inlet and continuously pass grade tertiary water (10 column volumes) into the column to keep the bed stable. 6.4.4 Sample determination
Accurately measure 50mL of Ni (NO) z standard solution, pass it through the column at a uniform speed, and immediately collect the effluent; then wash it with 50mL of grade tertiary water, collect the effluent at the same time, and mix all the collected effluents. The above collected Ni (NO:). The pH value of the effluent was adjusted to 7-8 with aqueous ammonia, 50 mL of ammonia-ammonium chloride buffer B and 0.25 g of murexamide indicator were added, and titrated with 0.1 mol/L EDTA standard solution until the solution changed from yellow to purple, which was the end point. Record the volume of EDTA standard solution consumed VEDTA.1. 6.4.5 Result calculation
Calculate according to formula (5):
Wherein:
VEDTA-I
PNet Ema VeVA 1 00
Metal chelate chromatography medium ligand density, in micromoles per milliliter (umol/mL); EDTA standard solution concentration, in moles per liter (mol/L); EDTA standard solution volume consumed by Ni(NO:)2 standard solution, in milliliters (mL); EDTA standard solution volume consumed by collected Ni(NO) effluent. in millimeters (mL); Metal chelate chromatography medium mass, in grams (g); Conversion factor for converting metal chelate chromatography medium mass into volume. The absolute difference between three independent determination results obtained under repeatability conditions shall not exceed 10% of the arithmetic mean. 6.5 Dynamic loading capacity
6.5.1 Solution preparation
6.5.1.1 Buffer A. pH 7.4
. (5)
Accurately weigh 5.80 g NazHPO,·12H,O, 0.59 g NaH,PO,·2HzO, 5.84 g NaCI and 3.40 g imidazole. Dissolve in grade tertiary water and adjust the pH to 7.4. Then make up to 1000 mL. Finally, filter with a 0.45 μm pore size filter membrane. 6.5.1.2 Buffer B. pH 7.4
Accurately weigh 2.90 g Na2HPO4·12H2O, 0.29 g NaHPO4.2H2O, 2.92 g NaCl and 17.02 g imidazole, dissolve them in grade III water, adjust the pH to 7.4, and then make up to 500 mL. Finally, filter with a 0.45 um pore size filter membrane. 6.5.1.3 His-tagged LDH sample (purity> 95 %) Weigh 300.0 mg His-tagged LDH lyophilized powder (lyophilized after dialyzing with secondary water, purity>95%), dissolve in 100 mL buffer A, concentration is 3.0 mg/mL, and calibrate the protein concentration according to the Coomassie Brilliant Blue method of the Pharmacopoeia of the People's Republic of China (2015 edition) (0731). Then filter with a 0.45 um pore size membrane
6.5.1.41% (volume fraction) acetone solution Accurately measure 0.1 mL acetone, add tertiary water to mix, and dilute to 10 mL. 6.5.2 Sample treatment
The method is the same as 6.1.1.
6.5.3 Sample loading
Select a chromatography column of Φ1.60cm×20.00cm, block the outlet of the column, pour the mixed slurry of medium and water into the chromatography column, let it stand, control the medium bed height to 5.00cm±0.20cm, and fill the upper end of the column with water. Open the column inlet, and continuously pass 10 column volumes of tertiary water into the column at a flow rate of 2.0mL/min. After the bed is stable, the test can be carried out. 6.5.4 Sample determination
Connect the chromatography column to the chromatography system, and detect the ultraviolet (UV) signal at 280nm to monitor the load determination process. The dynamic binding load is expressed as 50% penetration value. Measure and record the 100% UV signal of the sample His-tagged LDH, including the UV absorption of His-tagged LDH that is not bound to the medium. Use buffer A at a flow rate of 2.0 mL/min to balance the column to the UV baseline, load the sample at a flow rate of 2.0 mL/min, and finish loading when the UV signal concentration of His-tagged LDH in the flow-through curve is 50% of the sample concentration, and record the loading volume. After loading, use buffer A at a flow rate of 2.0 mL/min to balance the UV signal to the baseline: use buffer B at a flow rate of 2.0 mL/min to elute. Calculate the dynamic loading capacity. Determination of breakthrough volume under non-retention conditions: Connect the column to the chromatography system, detect the UV signal at 280 nm, load 10 μL of 1% acetone, and record the volume corresponding to the maximum UV signal. 6.5.5 Result expression
Calculate according to formula (6):
Wherein:
Q0% - Co(Vi- V)
Dynamic loading capacity of the medium, in milligrams per milliliter (mg/mL); Co
Starting protein concentration, in milligrams per milliliter (mg/mL); V
... (6)
—The volume of the effluent when the protein concentration C at the column outlet reaches 50% of the protein concentration C at the inlet, in milliliters (mL); V.
—Breakthrough volume under non-retention conditions, in milliliters (mL); Vael
—The volume of the medium, in milliliters (mL). The absolute difference between the three independent determination results obtained under repeatability conditions shall not exceed 10% of the arithmetic mean. 6.6 Total colony count
Sample pretreatment
The method is the same as 6.1.1.
6.6.2 Sample determination
GB/T38171—2019
Refer to the "Pharmacopoeia of the People's Republic of China" (2015 edition) (1105) Microbial limit test for non-sterile products - microbial count method. Take 1mL of the dried medium, add 1mL of grade 3 water, and mix the sample with a vortex mixer. Sterilize the conical flask containing 30mL of tryptic soy agar medium at 121.0℃ for 20min, put it in a 40.0℃ constant temperature box, and when the medium cools to 40.0℃. Use a micropipette to draw 1mL of the mixed sample and add it to the conical flask, mix it, pour the mixture into culture III, and cover it. Let the mixture solidify at room temperature. Place the culture blood in a constant temperature box at 35.0℃ for 5d. 6.6.3 Result calculation
Inspect culture III after the incubation period. Count the number of colony forming units (CFU). The results of three independent determinations obtained under reproducible conditions shall not exceed 5 CFU/mL of suspension. 6.75-Hydroxymethylfurfural shedding amount
6.7.1 Solution preparation
6.7.1.110% (volume fraction) methanol aqueous solution Accurately weigh 100mL of chromatographic pure anhydrous methanol, mix it evenly with 900mL of secondary water, and then filter it with a 0.22μm pore size filter membrane, and remove bubbles by ultrasonic.
6.7.1.25-Hydroxymethylfurfural standard stock solution Accurately weigh 20.0mg of 5-Hydroxymethylfurfural standard substance into a 100mL volumetric flask, dissolve it with 10mL of 10% methanol aqueous solution, make up to volume, and prepare a 0.20mg/mL standard stock solution. 6.7.1.3 1mmol/L hydrochloric acid solution. pH 3.0. Measure 0.083mL concentrated hydrochloric acid (12mol/L) and dilute to 1000mL, and adjust the pH to 3.0. 6.7.1.4 100mmol/L sodium hydroxide solution. pH 13.0. Accurately weigh 4.00g of sodium hydroxide solid, dissolve it in 100mL of tertiary water, cool to room temperature, and then dilute to 1000mL with tertiary water, and adjust the pH to 13.0.
6.7.1.5 Standard working solution
Pipette 5μL, 15μL, 25μL, 40μL, 50μL, 100μL, 1mL, 2mL of 5-hydroxymethylfurfural standard stock solution into 100mL volumetric flasks respectively, dilute to scale with 10% methanol aqueous solution, and prepare 0.01μg/mL, 0.03μg/mL, 0.05μg/mL, 0.08μg/mL, 0.10μg/mL, 0.20μg/mL, 1.00μg/mL, 2.00μg/mL standard working solutions. Prepare and use immediately. 6.7.2 Sample treatment
The cleaning method is the same as 6.1.1. Then take several 1.00g portions of the dried metal chelate chromatography medium and place them in glass test tubes with lids. Take 10mL of pH3.0 and pH13.0 solutions respectively and place them in each test tube. The sample tube was incubated at 40.0℃. After 7 days, the supernatant was transferred to a clean test tube.
The supernatant was evaporated by rotary evaporation (60.0℃, 50r/min). The volume was adjusted to 2mL, and an equal volume of 12mol/L hydrochloric acid was added, and hydrolyzed at 100.0℃ for 1h. The volume was adjusted to 5mL. Filtered with a 0.45μm filter membrane to obtain the sample solution. 6.7.3 Sample determination
High performance liquid chromatography conditions: The chromatographic column selected was Ci8, 5um, 250mmX4.6mm (inner diameter). The mobile phase was 10% methanol aqueous solution. GB/T38171—2019
Flow rate 1.0mL/min. Detection wavelength 285nm. Column temperature 30.0℃. Injection volume 10μL. The standard working solution and the sample solution were tested under the above high performance liquid chromatography conditions. Record the retention time and peak area of the standard working solution, and draw a standard working curve with the peak area versus the corresponding concentration. Use the retention time of the standard working solution to qualitatively characterize the sample, and record the peak area at the retention time, and use the standard working curve to quantitatively characterize the sample. 6.7.4 Calculation of results
Calculate according to formula (7):
Where:
X——the amount of 5-hydroxymethylfurfural released per milliliter of medium, in micrograms per milliliter (μg/mL); C
-the concentration of 5-hydroxymethylfurfural in the sample solution obtained from the working curve, in micrograms per milliliter (μg/mL); V
The final volume of the sample after hydrolysis with hydrochloric acid, in milliliters (mL); The mass of the metal chelate chromatography medium weighed, in grams (g); 1.4--Conversion factor for converting the mass of the metal chelate chromatography medium into volume The absolute difference between the three independent determination results obtained under repeatability conditions shall not exceed 10% of the arithmetic mean. 7 Inspection rules
7.1 Batch
Products with uniform quality produced in the same process cycle are considered a batch. 7.2
Perform in accordance with the provisions of GB/T5475.
Factory inspection
·(7)
Each batch of products shall be inspected before leaving the factory, and only qualified products may leave the factory. The factory inspection items are the particle size, maximum flow rate, ligand density, dynamic binding capacity and total colony count specified in Chapter 5. 7.4
Type inspection
During normal production, type inspection should be carried out every six months. Type inspection should be carried out in any of the following circumstances: 7.4.1
a) During trial production and appraisal of new products;
After normal production, when there are major changes in raw materials, processes, and equipment that may affect product performance; when production of a product is resumed after being suspended for more than half a year; c)
When there is a major difference between the factory inspection result and the last type inspection result; d)
When the supervisory agency makes a request.
7.4.2 Type inspection items are all items specified in Chapter 5 7.5
Judgment rules
Factory inspection judgment and re-inspection
Factory inspection items meet the requirements of the items in 7.3, and the batch is judged to be qualified 7.5.1.1
If 1 to 2 items of factory inspection items do not meet the requirements, they should be re-inspected. If there is still one item that does not meet the requirements after the re-inspection, the batch is judged to be unqualified.
If more than 2 items of factory inspection items do not meet the requirements, the batch is judged to be unqualified. 7.5.1.3
Type inspection judgment and re-inspection
Type inspection items meet the requirements of the items in 7.4 and are judged to be qualified GB/T38171—2019
If 1 to 3 (including 3 items) of type inspection items do not meet the requirements, they should be re-inspected. If there is still one item that does not meet the requirements after the re-inspection, the batch is judged to be unqualified.
If more than 3 items of type inspection fail to meet the requirements, the batch of products shall be deemed as unqualified. Labels, signs, packaging, transportation and storage 8.1
Should include at least the following contents:
Product name;
Model;
Volume;
Production batch number;
Production organization;
Production date;
Expiration date;
Precautions.
Packaging, storage and transportation labels shall comply with the provisions of GB/T191 8.3 Packaging
Plastic bottles should be used for packaging, and the packaging materials should ensure that the product is not contaminated or leaked during transportation and storage. 8.4 Transportation
Should be transported at room temperature, avoid overcooling or overheating, and take measures to prevent the product from losing water. 5 Purchase and storage
should be stored at 4℃～8℃ and has a validity period of five years. After the validity period, it can be retested according to the provisions of this standard. If the retest results meet the standard requirements, it can still be used.3 Sample determination
HPLC conditions: The chromatographic column is Ci8, 5um, 250mmX4.6mm (inner diameter). The mobile phase is 10% methanol in water. GB/T38171—2019
Flow rate 1.0mL/min. Detection wavelength 285nm. Column temperature 30.0℃. Injection volume 10μL. The standard working solution and the sample solution were tested under the above HPLC conditions. The retention time and peak area of the standard working solution were recorded, and the standard working curve was drawn with the peak area versus the corresponding concentration. The sample is qualitatively analyzed by the retention time of the standard working solution, and the area of the peak at the retention time is recorded. The sample is quantitatively analyzed by the standard working curve. 6.7.4 Calculation of results
Calculate according to formula (7):
Wherein:
X——the amount of 5-hydroxymethylfurfural released per milliliter of medium, in micrograms per milliliter (μg/mL); C
-the concentration of 5-hydroxymethylfurfural in the sample solution obtained from the working curve, in micrograms per milliliter (μg/mL); V
the final volume of the sample after hydrolysis with hydrochloric acid, in milliliters (mL); the mass of the metal chelate chromatography medium weighed, in grams (g); 1.4--the conversion factor for converting the mass of the metal chelate chromatography medium into the volume. The absolute difference between the three independent determination results obtained under repeatability conditions shall not exceed 10% of the arithmetic mean. 7 Inspection rules
7.1 Batch
Products with uniform quality produced in the same process cycle are considered a batch. 7.2
Perform in accordance with the provisions of GB/T5475.
Factory inspection
·(7)
Each batch of products shall be inspected before leaving the factory, and only qualified products may leave the factory. The factory inspection items are the particle size, maximum flow rate, ligand density, dynamic binding capacity and total colony count specified in Chapter 5. 7.4
Type inspection
During normal production, type inspection should be carried out every six months. Type inspection should be carried out in any of the following circumstances: 7.4.1
a) During trial production and appraisal of new products;
After normal production, when there are major changes in raw materials, processes, and equipment that may affect product performance; when production of a product is resumed after being suspended for more than half a year; c)
When there is a major difference between the factory inspection result and the last type inspection result; d)
When the supervisory agency makes a request.
7.4.2 Type inspection items are all items specified in Chapter 5 7.5
Judgment rules
Factory inspection judgment and re-inspection
Factory inspection items meet the requirements of the items in 7.3, and the batch is judged to be qualified 7.5.1.1
If 1 to 2 items of factory inspection items do not meet the requirements, they should be re-inspected. If there is still one item that does not meet the requirements after the re-inspection, the batch is judged to be unqualified.
If more than 2 items of factory inspection items do not meet the requirements, the batch is judged to be unqualified. 7.5.1.3
Type inspection judgment and re-inspection
Type inspection items meet the requirements of the items in 7.4 and are judged to be qualified GB/T38171—2019
If 1 to 3 (including 3 items) of type inspection items do not meet the requirements, they should be re-inspected. If there is still one item that does not meet the requirements after the re-inspection, the batch is judged to be unqualified.
If more than 3 items of type inspection fail to meet the requirements, the batch of products shall be deemed as unqualified. Labels, signs, packaging, transportation and storage 8.1
Should include at least the following contents:
Product name;
Model;
Volume;
Production batch number;
Production organization;
Production date;
Expiration date;
Precautions.
Packaging, storage and transportation labels shall comply with the provisions of GB/T191 8.3 Packaging
Plastic bottles should be used for packaging, and the packaging materials should ensure that the product is not contaminated and leaked during transportation and storage. 8.4 Transportation
Should be transported at room temperature, avoid overcooling or overheating, and take measures to prevent the product from losing water. 5 Purchase and storage
should be stored at 4℃～8℃ and has a validity period of five years. After the validity period, it can be retested according to the provisions of this standard. If the retest results meet the standard requirements, it can still be used.3 Sample determination
HPLC conditions: The chromatographic column is Ci8, 5um, 250mmX4.6mm (inner diameter). The mobile phase is 10% methanol in water. GB/T38171—2019
Flow rate 1.0mL/min. Detection wavelength 285nm. Column temperature 30.0℃. Injection volume 10μL. The standard working solution and the sample solution were tested under the above HPLC conditions. The retention time and peak area of the standard working solution were recorded, and the standard working curve was drawn with the peak area versus the corresponding concentration. The sample is qualitatively analyzed by the retention time of the standard working solution, and the area of the peak at the retention time is recorded. The sample is quantitatively analyzed by the standard working curve. 6.7.4 Calculation of results
Calculate according to formula (7):
Wherein:
X——the amount of 5-hydroxymethylfurfural released per milliliter of medium, in micrograms per milliliter (μg/mL); C
-the concentration of 5-hydroxymethylfurfural in the sample solution obtained from the working curve, in micrograms per milliliter (μg/mL); V
the final volume of the sample after hydrolysis with hydrochloric acid, in milliliters (mL); the mass of the metal chelate chromatography medium weighed, in grams (g); 1.4--the conversion factor for converting the mass of the metal chelate chromatography medium into the volume. The absolute difference between the three independent determination results obtained under repeatability conditions shall not exceed 10% of the arithmetic mean. 7 Inspection rules
7.1 Batch
Products with uniform quality produced in the same process cycle are considered a batch. 7.2
Perform in accordance with the provisions of GB/T5475.
Factory inspection
·(7)
Each batch of products shall be inspected before leaving the factory, and only qualified products may leave the factory. The factory inspection items are the particle size, maximum flow rate, ligand density, dynamic binding capacity and total colony count specified in Chapter 5. 7.4
Type inspection
During normal production, type inspection should be carried out every six months. Type inspection should be carried out in any of the following circumstances: 7.4.1
a) During trial production and appraisal of new products;
After normal production, when there are major changes in raw materials, processes, and equipment that may affect product performance; when production of a product is resumed after being suspended for more than half a year; c)
When there is a major difference between the factory inspection result and the last type inspection result; d)
When the supervisory agency makes a request.
7.4.2 Type inspection items are all items specified in Chapter 5 7.5
Judgment rules
Factory inspection judgment and re-inspection
Factory inspection items meet the requirements of the items in 7.3, and the batch is judged to be qualified 7.5.1.1
If 1 to 2 items of factory inspection items do not meet the requirements, they should be re-inspected. If there is still one item that does not meet the requirements after the re-inspection, the batch is judged to be unqualified.
If more than 2 items of factory inspection items do not meet the requirements, the batch is judged to be unqualified. 7.5.1.3
Type inspection judgment and re-inspection
Type inspection items meet the requirements of the items in 7.4 and are judged to be qualified GB/T38171—2019
If 1 to 3 (including 3 items) of type inspection items do not meet the requirements, they should be re-inspected. If there is still one item that does not meet the requirements after the re-inspection, the batch is judged to be unqualified.
If more than 3 items of type inspection fail to meet the requirements, the batch of products shall be deemed as unqualified. Labels, signs, packaging, transportation and storage 8.1
Should include at least the following contents:
Product name;
Model;
Volume;
Production batch number;
Production organization;
Production date;
Expiration date;
Precautions.
Packaging, storage and transportation labels shall comply with the provisions of GB/T191 8.3 Packaging
Plastic bottles should be used for packaging, and the packaging materials should ensure that the product is not contaminated and leaked during transportation and storage. 8.4 Transportation
Should be transported at room temperature, avoid overcooling or overheating, and take measures to prevent the product from losing water. 5 Purchase and storage
should be stored at 4℃～8℃ and has a validity period of five years. After the validity period, it can be retested according to the provisions of this standard. If the retest results meet the standard requirements, it can still be used.
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