| OBJECTIVE : To define the procedure for preparation and handling of General Reagents & Volumetric Solutions. This procedure is applicable to all types General Reagents & Volumetric Solutions prepared in Quality Control Laboratory. |
- RESPONSIBILITY:
Analyst is responsible for:
• To prepare the general reagent & volumetric solution as per approved template.
• To make entries of preparation and standardization in template as per SOP, also in expiry log.
•To make entries of expiry date in expiry log as per SOP,
• Any abnormality observed during preparation & standardization of general reagent & volumetric solution, immediate informed to the respective section Head.
• To destroy the solution as per schedule and SOP,
Reviewer/Section Head or Designee:
• To ensure availability of all solution preparation and standardization procedure,
•To ensure that proper practices arc followed as per SOP, while preparation and standardization of solution.
•To ensure that every solution arc prepared, used and discarded within scheduled time.
• To ensure proper labelling on the solution/reagents bottle.
To ensure all solution preparation and standardization records arc properly maintained.
To give training to all concern personnel before implementation of SOP
ACCOUNTABILITY:
The Head Quality Control is responsible for:
• To ensure the system implementation as per SOP.
The Head Quality Assurance is responsible for
• To ensure the system implementation as per SOP.
PROCEDURE
4.1 Test solution: Abbreviated as TS are solution of reagents in such solvents and of such definite concentrations as to be suitable for the specified purposes.
4.2 Primary standards: These are the materials which arc recommended for use as primary standards in the standardization of volumetric solutions and calibration of instrument.
4.3 Secondary standard: These are the materials which are used for preparation of volumetric solutions.
4.4 Volumetric solutions: These arc solutions of reagents of known concentrations intended primarily for use in quantitative determinations.
4.5 Reagents: Reagents arc substance used either as such or as constituent of solution required for various analysis.
4.6 Section Head / Reviewer or Designee shall issue the template to analyst if applicable
4.7 Template number of volumetric solution shall be given as VS/001/00
VS- Volumetric solution , 001- Serial number , 00- Revision number
4.8 Template number of reagent solution as follows as GR/001/00
GR-General Reagent , 001-Serial number, 00- Revision number
4.9 The Template Issuance number for the volumetric solution general as reagent solution
XX/YY/ZZZZ, where XX=Category of the solution, like VS= Volumetric solution, GR= General Reagent.
Example VS/24/0001, GR/24/0001
YY -stands for the last two digit of current year,
ZZZZ-Stands for four-digit serial number for particular section in a year
4.10 Analyst shall check the following things before preparation of any solution
4.11 The glassware being used is clean and dried
4.12 All required reagents are available
4.13 All required instrument are calibrated
4.14 Wear suitable safety appliances while making concentrated solutions of acid and alkali or any hazardous chemicals.
4.15 Analyst shall prepare all General Reagent & Volumetric as per respective template.
4.16 Coding System for General reagent solution & volumetric solution as follows-
4.17 Code No. for General reagent solution = GR/ XX/ YY/ ZZ and
Code No. for Volumetric Solution = VS/XX/YY/ZZ
Where,
GR- Standard for General reagent solution
VS-Stands for Volumetric Solution
XX- Stands for fixed serial number of particular solution
YY- Stands for the last two digit of current year. ZZ- Stands for number of that solution prepared during the year
4.17 Solution Logbook:
4.17.1 In case where template is required to issue, Section Head or Designee shall mention the “Code No”, “Template Issuance No”, “ Issued by & Date” and shall mentioned in “NA” in case of template is not available on the respective page for the solution allocated.
4.17.2 Analyst shall make entry on the respective page for the solution allocated.
4.17.3 Analyst shall make entry for “Code No”, “Preparation date”, “Weight taken”(shall mention the weight and name of the chemical used for weighing),”Volume made”,” Standardization date”, “ Page No”, “ Molarity/Normality” and submit for the review.
4.17.4 Sign of designated person shall put in “Checked by/date” column.
4.17.5 In case of any odd finding shall inform to section Head or Designee.
4.18 Labelling
4.18.1 Reagent Label is the identification tag for the respective solution, which shall be prepared at the time of preparation and standardization of the solution.
4.18.2 After completion of solution preparation, analyst shall prepare the label of respective solution for, “General Solution” Volumetric Solution”,” Indicator Solution”” Buffer Solution “and “Test Solution”
4.18.3 Analyst shall fill the details whichever is applicable “Name of Solution”, “Code No”, “Strength”,” Use before”, “Prepared by”, “Date of Preparation”,” Standardized by”,” Date of Standardization”.
4.18.4 Use green colour label for “General solution” red colour label for “Volumetric solution”, yellow colour for “Indicator solution”, blue colour label for “Buffer solution” and orange colour label for “Test solution”.
4.18.5 Analyst shall paste the label on the respective bottle.
4.18.6 Analyst shall check the Solution expiry for the solution to be discard and shall discard the solution as per the procedure verified by the second person.
4.19 General Guidelines for Volumetric Solutions
4.19.1 Analyst shall prepare all of Volumetric Solution as per respective template/ reference pharmacopeia.
4.19.2 Where Stabilization time is not given, stabilize the solution for one hour
4.19.3 Carry out the standardization of the Solution in triplicate with primary reference standard.
4.19.4 Check the variance between all finding if the observation RSD is more than 0.2% repeat the exercise and report the observation.
4.19.5 Also find out the mean Molarity/Normality, Which should be ±10% of the labelled Normality/Molarity.
4.19.6 In case of Molarity/Normality of prepared solution found more than 10%, carry out the restandardisation.
4.19.7 Write the weight taken, code no. of used instrument and other which is used for the preparation/standardization (wherever applicable) in template/ hard book.
4.19.8 Write the observed Molarity/Normality on the label as per Annexure and make necessary entries in hard book/ template. Shall submit the raw data to designated person for the checking.
4.19.9 Sign of designated person shall be put in “Checked by /date” Column.
4.19.10 In case of any odd finding shall inform to section Head / Head QC designee
4.19.11 Volumetric solution can be used within 1 month expiry except volumetric solution of Sodium hydroxide, Sodium thiosulphate and ferrous ammonium Sulphate which can be used within 15 days and all volumetric solution will be prepared as per requirement. In case, where extraneous matters, layer separation or hazy solution observed, do not use the solution and immediately report to Section Head/ QC Head and discard the solution.
4.19.12 The stability evaluation study of the volumetric solutions shall be done as per the protocol defined in Annexure
4.20 Usage of Primary and Secondary Standard
4.20.1 Section Head / Coordinator shall ensure the intactness and condition of the container at the time of receipt.
4.20.2 Use before date fell primary and Secondary standard shall be two years from the date of opening, where expiry date is not provided by the manufacturer.
4.20.3 Reviewer shall review the COA make sign and date on COA for correctness and completeness.
4.20.4 Coordinator shall allocate the Code No and mention it on the bottle label of standard and general coding system for primary standard.
4.20.5 Code No. =P/XX
Where XX = Standard for the serial number of primary Standard.
P = Stands for Primary Standard
4.20.6 General Coding System for the Secondary Standards.
Code No. =S/XX
Where,
XX- Stands for the Serial number of Primary Standard
S- Stands for Secondary Standard
make entry in Primary and Secondary usage log book (Annexure 2). Coordinator shall mention page number for respective primary and secondary standard in the index of usage logbook and “Mention the name of Standard”, “Code No” and use before date on the top of the page.
4.20.7 Use before date for primary and secondary standard shall be two years from the date of opening, where expiry date is not provided by the manufacture.
4.20.8 Analyst shall kept the primary and secondary standard at designated place as per storage condition mentioned on the container and update the list as per annexure
4.20.9 Analyst shall submit the log book to designated person for checking and checker shall make initial and date in “Checked by/ Date” Column.
4.21 General guidelines for reagent/ limit test solution
4.21.1 Analyst shall prepare all the General Reagents & Volumetric Solution as per respective template/reference pharmacopoeia.
4.21.2 Analyst shall check the sensitivity/standardize the solutions as per the defined procedure (wherever applicable).
4.21.3 Analyst shall write the weight taken, code no. of used instrument and others; which is used for the preparation/standardization (wherever applicable) in template
4.21.4 Analyst shall make necessary entries in the template. Shall submit the raw data to designated person for checking.
4.21.5 Sign of designated person shall put in “Checked by/date” column.
4.21.6 In case any abnormality observed informed to QC Head/ Designee
4.21.7 General Solution can be use within 2111011th and will be prepared as per requirement. In case, where extraneous matters, layer separation or hazy solution observed, do not use the solution and immediately report to Head QC.
4.22 General guideline for the solution Dissertation
4.22.1 Discard the excess solution after expiry / usage by diluting the solution with doubled quantity of water and then drain it into the drainage.
4.22.2 Solution can be discarded in case of specific instruction given.
4.23 Preparation of Volumetric Solutions
4.23.1 Ammonium Thiocyanate, 0.1M: Dissolve 1.903 g of ammonium thiocyanate in sufficient water to produce 250 ml. Standardize the solution in the following manner.
Pipette 30.0 ml of 0.1 M silver nitrate into a glass-stoppered flask, dilute with 50 ml of water, add 2 ml of nitric acid and 2 ml of ferric ammonium sulphate solution and titrate with the ammonium thiocyanate solution to the first appearance of a red-brown colour
Each ml of 0.1 M silver nitrate is equivalent 0.007612 g of NH4SCN.
4.23.2 Ceric Ammonium Sulphate, 0.1M; Ammonium Ceric Sulphate, 0.1M: Dissolve 16.25 g of ceric ammonium sulphate, with the aid of gentle heat, in a mixture of 7.5 ml of sulphuric acid and 125 ml of water. Cool, filter the solution, if turbid, and dilute to 250 ml with water. Standardize the solution in the following manner.
Transfer 0.2g of Sodium oxalate previously dried at 105̊C for 1 hour to a 250 ml conical flask. Dissolve in 100ml of water add 2ml of sulphuric acid
Take 25 ml the Sodium Thiosulphate solution add 0.35 gm of pure KI ,2 ml of 0.2 % starch solution, dilute to 250 ml and titrate with 0.1M Ceric Ammonium Sulphate to the permanent blue colour.Use V1S1 = V2S2 for calculating the factor of 0.1M Ceric Ammonium Sulphate soln.
4.23.3 Disodium Edetate, 0.1M: Dissolve 18.6 g of disodium edetate in sufficient water to produce 500 ml. Standardize the solution in the following manner. Weigh accurately about 0.8 g of granulated zinc, dissolve by gentle warming in 12 ml of dilute hydrochloric acid and 0.1 ml of bromine water. Boil to remove excess bromine, cool and add sufficient water to produce 200.0 ml. Pipette 20.0 ml of the resulting solution into a flask and nearly neutralize with 2M sodium hydroxide. Dilute to about 150 ml with water, add sufficient ammonia buffer pH 10.0 to dissolve the precipitate and add 5 ml in excess. Add 50 mg of mordant black IImixture and titrate with the disodium edetate solution until the solution turns green. Each ml of 0.1M disodium edetate is equivalent to 0.00654 g of Zn.
4.23.4 Ferrous Ammonium Sulphate, 0.1 M; Ammonium Iron(II) Sulphate, 0.1 M; Dissolve 10 g of ferrous ammonium sulphate in a previously cooled mixture of 10 ml of sulphuric acid and 50 ml of water, dilute with sufficient freshly boiled and cooled water to produce 250 ml. Standardize the solution in the following manner.
Measure accurately 25.0 ml of the solution into a flask, add 2 drops of 1,10-phenanthroline solution and titrate with 0.1 M ceric ammonium sulphate until the red colour is changed to pale blue. Each ml of 0.1 M ceric ammonium sulphate is equivalent to 0.03921g of Fe(NH4)2(SO4)2, 6H2O.
4.23.5 Hydrochloric Acid, 1M: Dilute 42.5 ml of hydrochloric acid with water to produce 500 ml. Standardize the solution in the following manner. Weigh accurately about 1.5 g of anhydrous sodium carbonate, previously heated at about 270° for 1 hour. Dissolve it in 100 ml of water and add 0.1 ml of methyl red solution. Add the acid slowly from a burette, with constant stirring, until the solution becomes faintly pink. Heat the solution to boiling, cool and continue the titration. Heat again to boiling and titrate further as necessary until the faint pink colour is no longer affected by continued boiling. Each ml of 1M hydrochloric acid is equivalent to 0.05299 g of Na2CO3.
4.23.6 Iodine, 0.05 M: Dissolve about 7 g of iodine in a solution of 18 g of potassium iodide in 50 ml of water, add 0.15 drops of hydrochloric acid and dilute with water to 500 ml. Standardize the solution in the following manner. Weigh accurately about 0.15 g of arsenic trioxide, previously dried at 105° for 1 hour, and dissolve in 20 ml of 1M sodium hydroxide by warming, if necessary. Dilute with 40 ml of water, add 0.1 ml of methyl orange solution and add dropwise dilute hydrochloric acid until the yellow color is changed to pink. Add 2 g of sodium carbonate, dilute with 50 ml of water and add 3 ml of starch solution. Titrate with the iodine solution until a permanent blue colour is produced. Each ml of 0.05 M iodine is equivalent to 0.004946 g of As2O3.
4.23.7 Perchloric Acid, 0.1 M: Mix 4.25 ml of perchloric acid with 250 ml of anhydrous glacial acetic acid and 12.5 ml of acetic anhydride, cool and add anhydrous glacial acetic acid to produce 500 ml. Allow the prepared solution to stand for 1 day for the excess acetic anhydride to be combined and carry out the determination of water. If the water content exceeds 0.05 %, add more acetic anhydride. If the solution contains no titrable water, add sufficient water to obtain a content of water between 0.02% and 0.05%. Allow the solution to stand for 1 day and again titrate the water content. The solution so obtained should contain between 0.02% and 0.05% of water. Standardize the solution in the following manner.
Weigh accurately about 0.35 g of potassium hydrogen phthalate, previously powdered lightly and dried at 120° for 2 hours and dissolve it in 50 ml of anhydrous glacial acetic acid. Add 0.1 ml of crystal violet solution and titrate with theperchloric acid solution until the violet colour changes to emerald-green. Peform a blank determination and make any necessary correction. Each ml of 0.1 M perchloric acid is equivalent to 0.02042 g of C8H5KO4.
Other strengths of perchloric acid should be prepared by diluting 0.1 M perchloric acid appropriately with anhydrous glacial acetic acid.
4.23.8 Potassium Hydroxide, 0.1 M: Dissolve about 3 g of potassium hydroxide in sufficient carbon dioxide free water to produce 500 ml. Standardize the solution in the following manner immediately before use.
Titrate 20.0 ml of the solution with 0.1 M hydrochloric acid using 0.5 ml of phenolphthalein solution as indicator. Each ml of 0.1 M hydrochloric acid is equivalent to 0.005611 g of KOH.
4.23.9 Silver Nitrate, 0.1 M: Dissolve 8.5 g in sufficient distilled water to produce 500 ml. Standardize the solution in the following manner.
Weigh accurately about 0.1 g of sodium chloride, previously dried at 110o for 2 hours and dissolve in 5 ml of water. Add 5 ml of acetic acid, 50 ml of methanol and 0.15 ml of eosin solution. Stir, preferably with magnetic stirrer, and titrate with the silver nitrate solution. Each ml of 0.1 M silver nitrate is equivalent to 0.005844 g of NaCl.
4.23.10 Sodium Hydroxide, 1M: Dissolve 21 g of sodium hydroxide in sufficient carbon dioxide-free water to produce 500 ml. Standardize the solution in the following manner immediately before use.
Weigh accurately about 5 g of potassium hydrogen phthalate, previously powdered and dried at 120o for 2 hours, and dissolve in 75 ml of carbon dioxide-free water. Add 0.1 ml of phenolphthalein solution and titrate with the sodium hydroxide solution until a permanent pink colour is produced. Each ml of 1M sodium hydroxide is equivalent to 0.2042 g of C8H5KO4.
Store in bottles with well-fitted suitable stoppers which prevent access to atmospheric carbon dioxide.
4.23.11 Sodium Thiosulphate, 0.1M: Dissolve 12.5 g of sodium thiosulphate and 0.1 g of sodium carbonate in carbon dioxide-free water and dilute to 500 ml with the same solvent. Standardize the solution in the following manner.
Dissolve 0.200 g of potassium bromate, weighed accurately, in sufficient water to produce 250.0 ml. To 50.0 ml of this solution add 2 g of potassium iodide and 3 ml of 2M hydrochloric acid and titrate with the sodium thiosulphate solution using starch solution, added towards the end of the titration, as indicator until the blue color is discharged. Each ml of 0.1M sodium thiosulphate is equivalent to 0.002784 g of KBrO3.
4.23.12 Sulphuric Acid, 0.5M: Add slowly, with stirring, 14 ml of sulphuric acid to about 500 ml of water, allow to cool 25ºC and standardize the solution in the following manner.
Weigh accurately about 1.5 g of anhydrous sodium carbonate, previously heated at about 270° for 1 hour. Dissolve it in 100 ml of water and add 0.1 ml of methyl red solution. Add the acid slowly from a burette, with constant stirring, until the solution becomes faintly pink. Heat the solution to boiling, cool and continue the titration. Heat again to boiling and titrate further as necessary until the faint pink colour is no longer affected by continued boiling. Each ml of 0.5M sulphuric acid is equivalent to 0.05299 g of Na2CO3.
4.23.13 Tetrabutylammonium Hydroxide, 0.1M: Dissolve 40 g of tetrabutylammonium iodide in 90 ml of dehydrated methanol in a glass-stoppered flask. Place in an ice-bath, add 20 g of powdered silver oxide, insert the stopper and agitate vigorously for 1 hour. Centrifuge a few ml, and test the supernatant liquid for iodides, Appendix 3.1. If the test is positive, add an additional 2 g of silver oxide and continue to stand for 30 minutes with intermittent agitation. When all of the iodide has reacted, filter through fine sintered-glass filter. Rinse the flask and filter with three quantities, each of 50 ml, of anhydrous toluene. Add the washings of the filtrate and dilute to 1000 ml with anhydrous toluene. Flush the solution for 10 minutes with dry, carbon dioxide-free nitrogen. Store in a container protected from carbon dioxide and moisture, and discard after 60 days.
Alternatively, prepare the solution by diluting a suitable volume of commercially available tetrabutylammonium hydroxide solution in methanol with a mixture of four volumes of anhydrous toluene and 1 volume of dehydrated methanol.
Standardize the solution in the following manner immediately before use.
Weigh accurately about 0.4 g of benzoic acid, dissolve in 80 ml of dimethylformamide, add a few drops of a 1% w/v solution of thymol blue in dimethylformamide and titrate with the tetrabutylammonium hydroxide solution to a blue end-point. Protect the solution from atmospheric carbon dioxide throughout the titration. Perform a blank determination and make any necessary correction. Each ml of 0.1M tetrabutylammonium hydroxide is equivalent to 0.01221 g of C7H6O2.
4.23.14 Zinc Sulphate, 0.1M: Dissolve 14.5 g of zinc sulphate in sufficient water to produce 500 ml. Standardize the solution in the following manner.
Take 20.0 ml solution into a 500 ml conical flask, add 5 ml of 2M acetic acid and dilute to 200 ml with water. Add about 50 mg of xylenol orange mixture and hexamethylenetetramine until the solution becomes violet-pink colour changes to yellow.1 ml of 0.1M disodium edetate is equivalent to 0.02875 g of ZnSO4, 7H2O.
5 REFERENCES:
IP and Inhouse
6. ABBREVIATION:
6.1 HDPE – High Density Polyethylene
6.2 SOP- Standard Operating Procedure
6.3 QC- Quality Control
6.4 TS- Test Solution
6.5 NIST- National Institute of Standard &
6.6 QA- Quality Assurance
6.7 RSD- Relative Standard Deviation