SANS 599-2009 Sterilized sodium chloride and dextrose intravenous infusion《无菌氯化钠和右旋糖静脉输液》.pdf

1、 Collection of SANS standards in electronic format (PDF) 1. Copyright This standard is available to staff members of companies that have subscribed to the complete collection of SANS standards in accordance with a formal copyright agreement. This document may reside on a CENTRAL FILE SERVER or INTRA

2、NET SYSTEM only. Unless specific permission has been granted, this document MAY NOT be sent or given to staff members from other companies or organizations. Doing so would constitute a VIOLATION of SABS copyright rules. 2. Indemnity The South African Bureau of Standards accepts no liability for any

3、damage whatsoever than may result from the use of this material or the information contain therein, irrespective of the cause and quantum thereof. ISBN 978-0-626-22693-0 SANS 599:2009 Edition 5.1SOUTH AFRICAN NATIONAL STANDARD Sterilized sodium chloride and dextrose intravenous infusion Published by

4、 SABS Standards Division 1 Dr Lategan Road Groenkloof Private Bag X191 Pretoria 0001 Tel: +27 12 428 7911 Fax: +27 12 344 1568 www.sabs.co.za SABS This standard may only be used and printed by approved subscription and freemailing clients of the SABS.SANS 599:2009 Edition 5.1 Table of changes Change

5、 No. Date Scope Amdt 1 2009 Amended to correct the formula for the calculation of the sodium chloride content in the product, and to update the subsequent numbering of the subclause (5.8.2). Foreword This South African standard was approved by National Committee SABS SC 1036A, Intravenous solutions,

6、 injectables and infusion sets Intravenous solutions and injectables, in accordance with procedures of the SABS Standards Division, in compliance with annex 3 of the WTO/TBT agreement. This document was published in March 2009. This document supersedes SANS 599:2008 (edition 5). A reference is made

7、in 6.2.1(m) to labelling required by “the current relevant national legislation“. In South Africa this means the Medicines and Related Substances Control Act, 1965 (Act No. 101 of 1965). Annex A forms an integral part of this standard. Annex B is for information only. A vertical line in the margin s

8、hows where the text has been technically modified by amendment No. 1. This standard may only be used and printed by approved subscription and freemailing clients of the SABS.SANS 599:2009 Edition 5.1 1 Contents Page Foreword 1 Scope . 3 2 Normative references. 3 3 Definitions 3 4 Requirements. 4 4.1

9、 Freedom from visible suspended matter and sediment 4 4.2 Fill volume . 4 4.3 pH value 4 4.4 Identification 4 4.5 5-Hydroxymethylfurfural and related substances 4 4.6 Dextrose content. 4 4.7 Sodium chloride content 5 4.8 Particulate matter (sub-visible particles) . 5 4.9 Sterility. 5 4.10 Bacterial

10、endotoxins 5 5 Inspection and methods of test 5 5.1 General 5 5.2 Inspection 5 5.3 Fill volume . 5 5.4 pH value 5 5.5 Identification 6 5.6 5-Hydroxymethylfurfural and related substances 7 5.7 Dextrose content. 7 5.8 Sodium chloride content 8 5.9 Particulate matter (sub-visible particles) . 9 5.10 St

11、erility. 9 5.11 Bacterial endotoxins 9 6 Packing and marking . 10 Annex A (normative) Sampling and compliance with this standard. 12 Annex B (informative) Quality verification of sterilized sodium chloride and dextrose intravenous infusion. 13 Bibliography. 13 This standard may only be used and prin

12、ted by approved subscription and freemailing clients of the SABS.SANS 599:2009 Edition 5.1 2 This page is intentionally left blank This standard may only be used and printed by approved subscription and freemailing clients of the SABS.SANS 599:2009 Edition 5.1 3 Sterilized sodium chloride and dextro

13、se intravenous infusion 1 Scope This standard covers chemical and biological requirements for a solution of sodium chloride and dextrose in water for injections that has been dispensed into suitable containers, sealed and sterilized. It also specifies the required marking. 2 Normative references The

14、 following referenced documents are indispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. Information on currently valid national and internat

15、ional standards can be obtained from the SABS Standards Division. 2.1 Standards SANS 1384, Plastics containers for parenteral solutions. SANS 3696/ISO 3696, Water for analytical laboratory use Specification and test methods. 2.2 Other publications British Pharmacopoeia (BP). United States Pharmacope

16、ia (USP). 3 Definitions For the purposes of this document, the following definitions apply. 3.1 acceptable acceptable to the authority administering this standard, or to the parties concluding the purchase contract, as relevant 3.2 batch that quantity of the product that is homogenous, filled and se

17、aled in containers, and sterilized in the same cycle of operations This standard may only be used and printed by approved subscription and freemailing clients of the SABS.SANS 599:2009 Edition 5.1 4 3.3 certified reagent for which a certificate of analysis stating the percentage purity is available

18、3.4 product sodium chloride and dextrose intravenous infusion that is filled, sealed and sterilized in the final container 4 Requirements 4.1 Freedom from visible suspended matter and sediment When examined in accordance with 5.2, the product shall be clear and colourless, and shall not contain any

19、antimicrobial agents nor any other added substances. Solutions containing 200 g or more of dextrose per litre shall not be more than faintly straw-coloured. 4.2 Fill volume 4.2.1 The maximum nominal fill volume of a container shall not exceed 1 L. 4.2.2 When determined in accordance with 5.3, the vo

20、lume of the contents of each container shall not be less than the nominal volume and not more than 110 % of the nominal volume. 4.3 pH Value When determined in accordance with 5.4, the pH value of the product shall be between 3,5 and 6,5. 4.4 Identification 4.4.1 Dextrose When tested in accordance w

21、ith 5.5.1, the product shall give a positive reaction for dextrose. 4.4.2 Sodium When tested in accordance with 5.5.2, the precipitate formed shall comply with the solubility tests in 5.5.2.2 that indicate the presence of sodium. 4.4.3 Chlorides When tested in accordance with 5.5.3, the product shal

22、l give a positive reaction for chlorides. 4.5 5-Hydroxymethylfurfural and related substances When tested in accordance with 5.6, the absorbance of the diluted product solution shall not exceed 0,25. 4.6 Dextrose content When determined in accordance with 5.7, the dextrose (C 6 H 12 O 6 ) content of

23、the product shall be between 95,0 % and 105,0 % of the concentration stated on the container or on the label. This standard may only be used and printed by approved subscription and freemailing clients of the SABS.SANS 599:2009 Edition 5.1 5 4.7 Sodium chloride content When determined in accordance

24、with 5.8, the sodium chloride (NaCl) content shall be between 95,0 % and 105,0 % of the concentration stated on the container or on the label. 4.8 Particulate matter (sub-visible particles) When tested in accordance with 5.9, the number of particles with a diameter 10 m and 25 m, respectively, shall

25、 comply with the limits for small volume injections and large volume injections, as relevant. 4.9 Sterility When tested in accordance with 5.10, there shall be no signs of microbial growth. 4.10 Bacterial endotoxins When tested in accordance with 5.11, the product shall not contain more than 10,0 US

26、P Endotoxin Units per gram of dextrose. 5 Inspection and methods of test 5.1 General Unless otherwise specified, only use water that complies with the requirements for grade 3 water as given in SANS 3696, and reagents of analytical reagent grade or of the purest grade available. 5.2 Inspection 5.2.1

27、 Gently invert the container and examine, without magnification, for any visible signs of suspended matter or sediment (see A.3). 5.2.2 Check for compliance with 4.1. 5.3 Fill volume 5.3.1 Transfer, as completely as possible, the contents of a container into a graduated measuring cylinder of a size

28、able to contain at least 110 % of the nominal volume of the container. 5.3.2 Record the volume of liquid in the measuring cylinder. 5.3.3 Determine the average fill volume of at least three containers. 5.3.4 Check for compliance with 4.2. 5.4 pH value 5.4.1 Dilute the product with water for injectio

29、ns or grade 3 water that complies with SANS 3696, if necessary, to contain not more than 5 g of dextrose per 100 mL. 5.4.2 Determine the pH value in accordance with the relevant procedure described in the current BP. This standard may only be used and printed by approved subscription and freemailing

30、 clients of the SABS.SANS 599:2009 Edition 5.1 6 5.4.3 Check for compliance with 4.3. 5.5 Identification 5.5.1 Dextrose 5.5.1.1 Reagents 5.5.1.1.1 Solution A Dissolve 3,466 g of cupric sulfate (CuSO 4 5H 2 O) in water and dilute to 50,0 mL with water. 5.5.1.1.2 Solution B Dissolve 17,3 g of crystall

31、ine potassium sodium tartrate (KNaC 4 H 4 O 6 4H 2 O) and 5 g of sodium hydroxide in water and dilute to 50,0 mL with water. 5.5.1.1.3 Cupric-tartaric solution Mix equal volumes of solution A and solution B immediately before use. 5.5.1.2 Procedure 5.5.1.2.1 Heat 5 mL of the cupric-tartaric solution

32、 in a test tube. Add a few drops of the product and heat again if necessary. 5.5.1.2.2 A copius red precipitate indicates the presence of dextrose. 5.5.1.2.3 Check for compliance with 4.4.1. 5.5.2 Sodium 5.5.2.1 Reagents 5.5.2.1.1 Absolute ethanol Analytical reagent grade of commerce that contains n

33、ot less than 99,5 % of ethanol (C 2 H 6 O) (volume fraction). 5.5.2.1.2 Methoxyphenylacetic reagent Dissolve 2,7 g of methoxyphenylacetic acid in 6 mL of tetramethylammonium hydroxide solution and add 20 mL of absolute ethanol. Store in a polyethylene container. 5.5.2.1.3 Ammonia solution, 5 M Dilut

34、e 37,5 mL of concentrated ammonia (about 13,5 M) to 100,0 mL with water. 5.5.2.1.4 Ammonium carbonate solution, 15,8 g/100 mL Dissolve 7,9 g of ammonium carbonate in water and dilute to 50,0 mL with water. 5.5.2.2 Procedure 5.5.2.2.1 Add 1,5 mL of the methoxyphenylacetic reagent to 0,5 mL of the pro

35、duct in a test tube and cool in ice water for 30 min. A voluminous white precipitate is formed. This standard may only be used and printed by approved subscription and freemailing clients of the SABS.SANS 599:2009 Edition 5.1 7 5.5.2.2.2 Place the test tube in water at 20 C and stir for 5 min. The p

36、recipitate does not disappear. 5.5.2.2.3 Add 1 mL of the ammonia solution. The precipitate dissolves completely. 5.5.2.2.4 Add 1 mL of the ammonium carbonate solution. No precipitate is formed. 5.5.2.2.5 Check for compliance with 4.4.2. NOTE Alternative methods for the identification of sodium can b

37、e used provided they give equivalent results. 5.5.3 Chlorides 5.5.3.1 Reagents 5.5.3.1.1 Nitric acid solution, c(HNO 3 ) = 2 mol/L Dilute 12,6 mL of concentrated nitric acid (d at 25 C = 1,42) to 100,0 mL with water. 5.5.3.1.2 Silver nitrate solution, 4,25 g/100 mL Dissolve 4,25 g of silver nitrate

38、(AgNO 3 ) in water and dilute to 100,0 mL with water. Ensure that the silver nitrate solution is clear before use, and filter if necessary. Store protected from light. 5.5.3.2 Procedure 5.5.3.2.1 Transfer 2 mL of the product into a 50 mL centrifuge tube. 5.5.3.2.2 Add one drop of the nitric acid sol

39、ution and 0,4 mL of the silver nitrate solution. Shake and allow to stand. A curdled white precipitate is formed. 5.5.3.2.3 Centrifuge the tube with the contents. Wash the precipitate three times with 1 mL of water. Carry out this operation rapidly in subdued light, disregarding the fact that the su

40、pernatant might not become perfectly clear. 5.5.3.2.4 Suspend the precipitate in 2 mL of water and add 1,5 mL of concentrated ammonia. The precipitate dissolves easily with the exception of a few large particles, which dissolve slowly. 5.5.3.2.5 Check for compliance with 4.4.3. 5.6 5-Hydroxymethylfu

41、rfural and related substances 5.6.1 Dilute a volume of the product containing 1,0 g of dextrose (C 6 H 12 O 6 ) to 500 mL with water. 5.6.2 Measure the absorbance of this solution at the maximum at approximately 284 nm in a 1 cm cell with water in the reference cell. 5.6.3 Check for compliance with

42、4.5. 5.7 Dextrose content 5.7.1 Apparatus Polarimeter, capable of giving readings to the nearest 0,01 . This standard may only be used and printed by approved subscription and freemailing clients of the SABS.SANS 599:2009 Edition 5.1 8 5.7.2 Reagent Ammonia solution, 5 M Dilute 37,5 mL of concentrat

43、ed ammonia (about 13,5 M) to 100,0 mL with water. 5.7.3 Procedure 5.7.3.1 Pipette a volume of the product containing 2 g to 5 g of dextrose into a 100,0 mL volumetric flask. 5.7.3.2 Add 0,2 mL of the ammonia solution and dilute to 100,0 mL with water. Mix well and leave for 30 min. 5.7.3.3 Determine

44、 the optical rotation (R) at (20 0,5) C in a 200 mm tube with the polarimeter using sodium light. 5.7.3.4 Calculate the dextrose content (D) of the product, in g/100 mL, using the following formula D = V R 100 0,9477 where R is the observed optical rotation, in degrees; V is the volume of the produc

45、t used for the test, in millilitres. The observed rotation multiplied by 0,9477 represents the mass of dextrose (C 6 H 12 O 6 ), in grams, in the volume (V) used for the test. 5.7.3.5 Check for compliance with 4.6. 5.8 Sodium chloride content 5.8.1 Reagents 5.8.1.1 Silver nitrate solution, c(AgNO 3

46、) = 0,1 mol/L Dissolve 17,0 g of silver nitrate (AgNO 3 ) in water and dilute to 1 L with water. Standardize against certified sodium chloride and store protected from light. NOTE 1 Commercially available concentrated volumetric solutions can also be used provided the diluted solutions are standardi

47、zed before use. NOTE 2 The methods for standardization given in the USP or in the BP can be used. 5.8.1.2 Potassium chromate solution, 5 g/100 mL Dissolve 5 g of potassium chromate (K 2 CrO 4 ) in water and dilute to 100,0 mL with water. Potassium chromate produces a red precipitate with silver nitr

48、ate in neutral solutions. This standard may only be used and printed by approved subscription and freemailing clients of the SABS.SANS 599:2009 Edition 5.1 9 5.8.2 Procedure 5.8.2.1 Transfer a volume of the product that contains approximately 0,1 g of sodium chloride into a conical flask and add abo

49、ut 1 mL of the potassium chromate solution. 5.8.2.2 Titrate with the standardized silver nitrate solution to a reddish brown endpoint. 5.8.2.3 Calculate the sodium chloride content (S) in the product, in g/100 mL, using the following formula S = 1000 100 58,44 V M tAmdt 1 where t is the volume of silver nitrate used in the titration, in millilitres; M is the molarity of the standardized silver nitrate solution; 58,44 is the molecular mass of sodium chloride (NaCl); Amdt 1 V is the volume of product used for the test, in millilitres. 5.8.2.4 Alternatively, the s