GB/T 14233.1-2008Test Methods for Infusion, Transfusion, Injection Equipment for Medical Use — Part 1: Chemical Analysis Methods

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Foreword

GB/T 14233 Test Methods for Infusion, Transfusion, and Injection Equipmenst for Medical Use consists of two parts: - Part 1: Chemical Analysis Methods; and - Part 2: Biochemical Test Methods. This standard is Part 1 of GB/T 14233. The Standard replaces GB/T 14233.1 – 1998 Test Methods for Infusion, Transfusion, and Injection Equipmenst for Medical Use Part 1: Chemical Analysis Methods. Given that GB/T 14233.1 – 1998 has been widely quoted in many product standards, the clause numbers in this Standard are kept as closely as possible to the original standard to avoid confusions caused by the change of clause No. in standard revision. The original clauses are altered wherever the alteration is necessary, and new amendments, followed by new methods, are numbered on the basis of the original serial number. The Standards, as compared with GB/T 14233.1 – 1998, is mainly changed as follows: - Solution Preparation methods and their description are revised; - Two test solution preparation methods are added: one for irregular shaped and bulky products with short using time (less than 24 hours), another for irregular shaped products with long using time (more than 24 hours) and water-absorbing materials; - Test methods for turbidity, color and luster are added; - Test methods for the determination of chloride, pH value, heavy metal, ammonium, zinc, burning residue and residual ethylene oxide are revised; - Test methods for atomic fluorescence spectrophotometry is added; and - Test methods for sulfate are deleted. The Standard is brought up by the State Food and Drug Administration. The Standard resides with the National Standardization Technical Committee for Transfusion Equipments. The Standard was mainly drafted by: Jinan Medical Device Testing Center, State Food and Drug Administration Primary drafters of the Standard: Luo Hongyu, Pan Huaxian, Shi Yanping, Sun Guangyu, Li Kefang, Qin Dongli, Liu Bin, Liu Lili, and Guo Lun. Replaced previous editions by the Standard are: - GB/T 14233. 1 – 1993; and - GB/T 14233. 1 – 1998.

1 Scope

Test methods for chemical analysis of infusion, transfusion, injection equipments for medical use are specified in this part of Standard GB/T 14233. This part of Standard applies to chemical analysis of infusion, transfusion, injection and attached equipments for medical use that are made of medical polymer materials. Chemical analysis of other medical polymer products can also refer to this Standard.

2 Referenced Standards

This part of Standard GB/T 14233 incorporates clauses of the following documents if they are quoted. If the references are dated, all the following lists of modifications (errata excluded) or revised editions thereof shall not be applicable to the Standards. However, parties concerned that have reached an agreement based on the Standards are encouraged to hold discussions on whether the latest editions of the said references can be adopted. Where the references are undated, the updated editions thereof shall apply to the Standards. GB/T 601 Chemical Reagents - Preparation of Standard Titrating Solution GB/T 6682 Specifications on Water for Analytical Laboratory and Test Methods (GB/T 6682 – 2008, ISO 3696: 1987, MOD) Pharmacopoeia II of the People’s Republic of China (2005 edition)

3 General Principles

3.1 All the analysis in the Standard is performed by two parallel test groups and the results should be within permissible relative deviation limits. The arithmetic average is used as experimental result. If only one test is qualified and the other one is not qualified, the arithmetic average calculation can’t be calculated and the test should be performed again. 3.2 All the reagents in the Standard, unless specified otherwise, are all analytically pure. 3.3 Water for test use in the Standard, unless specified otherwise, should meet requirements for level II water in GB/T 6682.

3.4 The glossary ‘room temperature’ in the Standard refers to 10 – 30℃. 3.5 The glossary ‘precisely weigh’ in the Standard indicates weighing in precision 0.1mg. 3.6 The glossary ‘precisely measure’ in the Standard indicates measuring with transfer pipettes that meet the accuracy requirements specified in relevant national standards. 3.7 Weight law of permanence indicates weight difference of the test product after two times burning or drying is no more than 0.3mg. 3.8 All the glass containers in the Standard, unless specified otherwise, are all silicon borate glass containers.

4 Preparation of Test Solution

4.1 When preparing test solution, it’s required to simulate as much as possible the conditions products undergo in use (such as application area, time, temperature, etc.). If using time of the product is a little long (more than 24h), it’s recommended to prepare the test solution under accelerated test condition, but feasibility and reasonability of the methods should be verified. 4.2 The method of preparing test solution should be those that try every means to make all measurable surfaces of the samples extracted. 4.3 It’s recommended to choose preparation methods of test solution from Table 1. 1 3 sets of samples are chosen and they’re connected to be a circular system with a glass flask. 250mL water is added and kept at temperature of 37℃±1℃. Through a wiggly pump operating on a silicon rubber tube for medical use, which is as short as possible, water is circulated at 1L/h for 2h. All liquid is collected and cooled to room temperature, which is to be used as test solution. Water of the same volume is placed into glass flask. Blank control solution is prepared according to the same method. glass container. Add water and make sure that the ratio of entire surface area of inside and outside sample (cm2) and In vivo catheters with short using time (no more water (ml) is 2:1. With container cover, it is stored at 37℃±1℃ for 24h. Separate the sample from the solution and cool the solution to room temperature which is to be used as test solution. Water of the same volume is placed into glass container. Blank control is prepared according to the same method. into fragments of 1cm2. Wash them with water and dry them. Then, put them into a glass container. Add water and make sure that the ratio of entire surface area of inside and outside sample (cm2) and water (ml) is 5:1(or 6:1). With container cover, it is placed into Pressure Steam Sterilizer. Heat it with temperature of 121℃±1℃ for 30min. After heating, separate the sample from the solution and cool the solution to room temperature which is to be used as test solution. Water of the same volume is placed into glass container. […]

5 Analytical Methods for Test Solution Extraction

5.1 Turbidity, color and luster 5.1.1

5.1.1.1 Preparation of solution

Hydrazine sulfate solution: take 1.00g hydrazine sulfate dried to constant weight at temperature of 105℃ into glass flask, add water to be dissolved and then diluted to scale, shake up, and stand for 4h to 6h. Methenamine solution: dissolve 2.5g methenamine with 25mL water in 100mL glass flask with plug. Primary lactescent suspension: add 25mL hydrazine sulfate solution into methenamine solution; mix them and stand for 24h. […]

5.1.1.2 Test process

5.1.1.2.1 Method I

Use bottom-flatted neutral glass test tube that is colorless and transparent, with 15mm – 25mm inner diameter to compare the test solution with the control suspension. The liquid in the test tube shall be 40mm in layer depth. Stand the prepared control suspension for 5min, and then observe the solution vertically to a black background in diffused sunlight.

5.1.1.2.1 Method II

Under room temperature condition, place the test solution and equivalent control suspension respectively into a bottom-flatted neutral glass test tube that is colorless and transparent, with 15mm – 25mm inner diameter. Stand the prepared control suspension for 5min, and then observe and compare horizontally the solution, which is placed together with the test solution right below the umbrella lamp, with intensity of illumination being 1000 lx. It shall be performed according to Annex IX A Inspection Techniques of Solution Color in the Pharmacopoeia II of the People’s Republic of China (2005 edition).

5.2 deoxidized substance (active oxidized substance) 5.2.1

5.2.1.1 Principle

Potassium permanganate is strong oxidant. In acid medium, potassium permanganate and deoxidized substance react, during which MnO _ 4 is deoxidized to Mn2+： MnO

5.2.1.2 Preparation of solution

Sulfate solution: take out 128mL sulfate, which is then slowly poured into 500mL water. Cool and then dilute the solution to 1000Ml. Sodium oxalate solution [c(2Na2C2O4)=0.1mol/L]: take out 6.00g sodium oxalate, which is dried to constant weight at temperature of 105 – 110℃. Add water to dissolve and dilute the solution to 1000mL. Sodium oxalate solution [c(1/2Na2C2O4)=0.01mol/L]: Before use, take out sodium oxalate solution [c(1/2Na2C2O4)=0. […]

5.2.1.4 Result calculation

Content of deoxidized substance (active oxidized substance) is expressed as the consumed standard potassium permanganate solution, which is calculated as formula (1) indicates：

5.2.2.1 Principle

The deoxidized substance contained in water solution, in case of acid condition, and if heated, will be oxidized by potassium permanganate. Potassium iodide is oxidized to iodide by excessive potassium permanganate. And iodide is deoxidized by hyposulphite.

5.6 Total heavy metal content 5.6.1

5.9 Some heavy metal element 5.9.1

5.9.2.1 Zinc

5.9.2.2 Lead

6 Analytical Methods for Total Heavy Metal Content

6.2 Reagent and preparation of solution

It shall be performed according to 5.6.1.2.

6.3 Preparation of test solution

Take 1- 2g sample and cut it into fragments of 5.mm×5mm. Place them into a porcelain crucible and heat slowly in order to make it completely charred; after cooling, add 0.5 – 1mL sulfate to wet it. Heat at a low temperature until there is no sulfate vapor; then, add 0.5mL nitric acid, evaporate to dryness and cool after vapor of nitrogen oxide is removed completely. Burn it at 500℃ - 600℃ to incineration; after cooling, add 2mL hydrochloric acid, and then it is placed into water bath to be braised. Afterwards, add 15mL water, and then add 1 drop of phenolphthalein reagent, followed by drops of ammonia reagent, until the above solution turns slight red. Add 2mL acetate buffer solution (pH 3.5), and after being slightly heated to dissolve, transfer the solution into a 25mL Nessler colorimetric tube, in which water is added to make it 25mL test solution. Place another porcelain crucible, in which 0.5 - 1mL nitric acid, 0.5mL nitric acid and 2mL hydrochloric acid are added, into the water bath in order to be braised. Then, add 2mL acetate buffer solution (pH 3.5) and 15mL water; after being slightly heated to dissolve, transfer the solution into a 25mL Nessler colorimetric tube, in which a certain amount of standard lead solution is added, and then dilute it with water to 25mL, which is used as the standard comparison solution.

6.4 Test process

Add 2mL thioacetamide reagent in each of the test solution and the standard comparison solution. Shake it up and let it where it is for 2min. Under white background, observe from the upper side and compare the colors. […]

7 Analytical Methods for Element Content of Some Heavy Metal

7.2 Colorimetric methods 7.2.1

Take 1- 2g sample and cut it into fragments of 5.mm×5mm. Place them into a porcelain crucible and heat slowly in order to have it completely charred; after cooling, add 0.5 – 1mL sulfate to wet it. Heat at a low temperature until there is no sulfate vapor; then, add 0.5mL nitric acid to be braised; cool after vapor of nitrogen oxide is removed completely. Burn it at 500℃ - 600℃ to incineration; after cooling, add 2mL hydrochloric acid, and then it is placed into water bath to be braised. Afterwards, add 15mL water, and then add1 drop of phenolphthalein reagent, followed by drops of ammonia reagent, until the above solution turns slight red. Finally water is added to make it 25mL test solution. The blank comparison solution is prepared according to the same method. Take test solution and blank comparison solution. Go on based on methods prescribed in Take test solution and blank comparison solution. Go on based on methods prescribed in

7.3 Atomic fluorescence spectrometry 7.3.1

7.3.1.1 Wet digestion: accurately weigh 2g sample and cut it into fragments of 5mmⅹ5mmm; place them into a 100mL conical flask, add 30mL nitric acid and 1.25ml sulfate; shake it up and then stand it for one night; place it on an electric warming plate to be heated for digestion. If there still are substances not decomposed in the digestion solution or the digestion solution turns darker in color when only about 10mL left, take it down and add 5 -10mL nitric acid to be digested to 10mL again and observe; repeat this two or three times. Make sure the solution is not charred. After cooling, add 25mL water to be braised again until sulfate vapor appears. Cool it again, transfer the substance into a 50mL volumetric flask by using water, and add water to make it 50mL test solution. The blank comparison solution is prepared via the same method. 7.3.1.2 Dry charring: take 1 - 2g sample accurately weighed into a crucible; add 10mL magnesium nitrate solution with the mass concentration of 150g/L, mix it up and braise it at a low temperature; carefully cover the dry residue with 1g magnesium oxide to be charred until there is no black smoke; […]

8 Burning Residue

8.1 Test process

Take.2g - 5g sample and cut it into 5mm x 5mm. Place it into the crucible, which has been burnt to constant weight. Weigh in precision. Burn the sample slowly in ventilating cabinet until it is totally charred. After cooling, add 0.5mL - 1mL sulfate to humidify it. Heat it at a low temperature until sulfate vapor is removed completely. Burn at 700℃ - 800℃ until it is totally incinerated. Place it in a drier until it reaches room temperature. Weigh it and burn it at 700℃ - 800℃ to constant weight again. If residue is preserved for the measurement of heavy metal, the burning temperature shall be controlled within the range of 500 - 600℃.