Get the latest updates from us for free

Method of Analysis for Lithium Carbonate


Procedure for the analysis of the Lithium Carbonate in quality control laboratory in pharmaceuticals.
1. Description
A white powder.

2. Solubility
Slightly soluble in water, practically insoluble in alcohol.

3. Identification
A. When moistened with hydrochloric acid, it gives a red color to a non-luminous flame.
B. Dissolve 0.2 g in 1 ml of hydrochloric acid. Evaporate to dryness on a water-bath. The residue dissolves in 3 ml of alcohol.
C. Introduce into a test tube 0.1 g of the sample. Add 3 ml of 2M acetic acid, close the tube immediately using a stopper fitted with a glass tube bent at two right angles. The solution or suspension effervesces evolving a colorless and odorless gas. Heat gently and collect the gas in 5 ml of 0.1M barium hydroxide. A white precipitate is produced which dissolves on the addition of an excess of 7M hydrochloric acid.         

4. Appearance of Solution
Limit: Solution S is clear and colorless.
Clarity of The Solution:
Sample Preparation: (Solution S) Suspend 10.0 g in 30 ml of distilled water and dissolve by the addition of 22 ml of nitric acid. Add dilute sodium hydroxide solution until the solution is neutral and dilute to 100 ml with distilled water.
Standard Preparation: Dissolve 1.0 g of hydrazine sulfate in sufficient water to produce 100.0 ml and allow standing for 4 to 6 hours. Add 25.0 ml of this solution to a solution containing 2.5 g of hexamine in 25.0 ml of water mix well and allow standing for 24 hours. To prepare the standard of opalescence, dilute 15.0 ml of the suspension to 1000.0 ml with water.
Into separate matched, flat-bottomed test tubes, 15 to 25 mm in internal diameter and of colorless, transparent, neutral glass, place sufficient of the solution being examined and of the appropriate reference suspension, such that the test tubes are filled to a depth of 40 mm. Five minutes after preparation of the reference suspension, compare the contents of the test tubes against a black background by viewing in diffused daylight down the vertical axes of the tubes.
Color of the Solution:
Sample Preparation: Solution S
Standard Solution: Water
Using identical tubes of colorless, transparent, neutral glass with a flat base and an internal diameter of 15 to 25 mm compare a 40-mm layer of the liquid being examined with a 40-mm layer of water. Examine the columns of liquid in diffused daylight by viewing down the vertical axes of the tubes against a white background.

5. Chlorides
Limit: Not more than 200 ppm.
Procedure
2.5 ml of solution S diluted to 15 ml with water. To this solution add 1 ml of 2M nitric acid, pour the mixture as a single addition into 1 ml of silver nitrate solution and allow standing for 5 minutes protected from light. When viewed transversely against a black background any opalescence produced is not more intense than that obtained by treating a mixture of 10 ml of chloride standard solution (5 ppm Cl) and 5 ml of water in the same manner.

6. Sulphate
Limit: Not more than 200 ppm.
Procedure
Sample Preparation: Disperse 1.25 g in 5 ml of distilled water and dissolve by adding 5 ml of hydrochloric acid. Boil for 2 min. Cool and add dilute sodium hydroxide solution until neutral. Dilute to 25 ml with distilled water.
Add 1 ml of a 25% w/v solution of barium chloride to 1.5 ml of sulfate standard solution (10 ppm SO4), shake and allow standing for 1 minute. Add 15 ml of sample preparation and 0.5 ml of 5M acetic acid and allow standing for 5 minutes. Any opalescence produced is not more intense than that of a standard prepared in the same manner but using 15 ml of sulfate standard solution (10 ppm SO4) in place of the solution being examined.

7. Arsenic
Limit: Not more than 2 ppm.
Procedure
The apparatus consists of a 100-ml conical flask closed with a ground-glass stopper through which passes a glass tube about 200 mm long and 5 mm in internal diameter. The lower part of the tube is drawn to an internal diameter of 1.0 mm and 15 mm from its tip is a lateral orifice 2 to 3 mm in diameter. When the tube is in position in the stopper the lateral orifice should be at least 3 mm below the lower surface of the stopper. The upper end of the tube has a perfectly flat, ground surface at right angles to the axis of the tube. A second glass tube of the same internal diameter and 30 mm long, with a similar flat ground surface, is placed in contact with the first and is held in position by two spiral springs. Into the lower tube insert 50 to 60 mg of lead acetate cotton, loosely packed, or a small plug of cotton and a rolled piece of lead acetate paper weighing 50 to 60 mg. Between the flat surfaces of the tubes place a disc or a small square of mercury (II) bromide paper large enough to cover the orifice of the tube (15 mm × 15 mm).
In the conical flask dissolve 0.5 gm of sample in 25 ml of water. Add 15 ml of hydrochloric acid, 0.1 ml of tin (II) chloride solution AsT and 5 ml of potassium iodide solution, allow standing for 15 minutes and adding 5 g of activated zinc. Immediately assemble the two parts of the apparatus and immerse the flask in a water bath at a temperature such that a uniform evolution of gas is maintained. After not less than 2 hours any stain produced on the mercury (II) bromide paper is not more intense than that obtained by treating 1 ml of arsenic standard solution (1 ppm As) diluted to 25 ml with water in the same manner.

8. Calcium
Limit: Not more than 200 ppm.
Procedure
Sample Preparation: 5 ml of solution S diluted to 15 ml with distilled water.
To 0.2 ml of alcoholic calcium standard solution (100 ppm Ca) add 1 ml of ammonium oxalate solution. After 1 minute add a mixture of 1 ml of 2M acetic acid and 15 ml of sample preparation and shake. After 15 minutes any opalescence produced is not more intense than that of a standard prepared in the same manner using a mixture of 10 ml of calcium standard solution (10 ppm Ca) and 5 ml of water in place of the solution of the substance being examined.

9. Heavy metals
Limit: Not more than 20 ppm.
Procedure
To 12 ml of Solution S add 2 ml of acetate buffer pH 3.5, mix, add to 1.2 ml of Thioacetamide reagent, mix immediately and allow standing for 2 minutes. Any brown color produced is not more intense than that obtained by treating, in the same manner, a mixture of 10 ml lead standard solution (2 ppm Pb), and 2 ml of the solution being examined. The standard solution exhibits a slightly brown color when compared to a solution prepared by treating, in the same manner, a mixture of 10 ml of water and 2 ml of the solution being examined.

10. Iron
Limit: Not more than 20 ppm.
Procedure
Test Preparation: 5 ml of solution S diluted to 10 ml with water
Transfer sample preparation to a Nessler cylinder. Add 2 ml of a 20% w/v solution of citric acid and 0.1 ml of mercaptoacetic acid, mix, make alkaline with 10M ammonia, dilute to 20 ml with water and allow standing for 5 minutes. Any pink color produced is not more intense than that obtained by treating 10 ml of iron standard solution (1 ppm Fe) in the same manner.

11. Magnesium
Limit: Not more than 150 ppm.
Procedure
Test Preparation: Dilute 1 ml of solution S to 10 ml with water. 6.7 ml of this solution diluted to 10 ml with water.
To 10 ml of test preparation add 0.1 g of sodium tetraborate. Adjust the pH of the solution, if necessary, to 8.8 to 9.2 with 2M hydrochloric acid or 2M sodium hydroxide. Shake with two 5-ml quantities of a 0.1% w/v solution of 8-hydroxyquinoline in chloroform, shaking for 1 minute, allowing to stand, separating and discarding the organic layer each time. To the aqueous layer add 0.4 ml of n-butylamine and 0.1 ml of triethanolamine. Adjust the pH of the solution, if necessary, to 10.5 to 11.5. Add 4 ml of the solution of 8-hydroxyquinoline, shake for 1 minute, allow to stand and separate. Any color produced in the lower layer is not more intense than that obtained by treating a mixture of 1 ml of magnesium standard solution (10 ppm mg) and 9 ml of water in the same manner.

12. Potassium
Limit: Not more than 300 ppm.
Procedure
Determined by atomic emission spectrometry
Test solution: Dissolve 1.0 g of the substance to be examined in 10 ml of hydrochloric acid and dilute to 50.0 ml with water.
Reference solutions: Prepare the reference solutions using a solution of potassium chloride R containing 500 mg of K per milliliter, diluted as required. Measure the emission intensity at 766.5 nm.

13. Sodium
Limit: Not more than 300 ppm.
Procedure
Determined by atomic emission spectrometry.
Test solution: Dissolve 1.0 g of the substance to be examined in 10 ml of hydrochloric acid and dilute to 50.0 ml with water.
Reference solutions: Prepare the reference solutions using a solution of sodium chloride R containing 500 mg of Na per milliliter, diluted as required. Measure the emission intensity at 589 nm.

14. Loss on Drying
Limit: Not more than 1.0%
Procedure
Weigh 1.000 g of substance in a clean and dried pre-weighed LOD Bottle. Cover the stopper and gently shake to distribute material to not more than 10 MM height. Place the LOD Bottle in the oven and remove the cover and leave it also inside the oven. Dry the sample at 200° C for 4 hr. On opening the chamber, immediately close the LOD Bottle, transfer it to desiccators and bring it to room temperature.  
Calculation:

                                     W2 – W1
% Loss on Drying = --------------- X 100
                                     W2 – W3
Where: 
W1 = Weight of empty clean and dried LOD Bottle.
W2 = Weight of LOD Bottle + sample.
W3 = Weight of LOD Bottle + sample. (After drying)

15. Insoluble Substances
Limit: Weight of the residue is not more than 0.02% of the weight of Lithium Carbonate taken.
Procedure
Transfer 10 g sample to a 250-ml beaker, add 50 ml of water, then add slowly 50 ml of 6 N hydrochloric acid. Cover with a watch glass, and boil the solution for 1 hour. Filter the solution through a dried, tarred filtering crucible fitted with a glass-fiber filter disk, using suction. Wash the filter with hot water until the last washing is free from chloride when tested with silver nitrate. Dry the crucible in an oven at 110° for 1 hour: the weight of the residue is not more than 0.02% of the weight of Lithium Carbonate taken.

16. Aluminum
Limit: No turbidity or precipitate will observe.
Procedure
Dissolve 500 mg sample in 10 ml of water by the dropwise addition, with agitation, in hydrochloric acid. Boil the solution, then cool it, and to 5 ml of the solution add 6 N ammonium hydroxide until the reaction is alkaline: no turbidity or precipitate is observed.

17. Organic Volatile Impurity
Limit: Chloroform: Not more than 60 ppm.
1,4 Dioxane: Not more than 380 ppm.
Methylene Chloride: Not more than 600 ppm.
Trichloroethylene: Not more than 80 ppm.
Procedure:
A gas chromatograph capable of temperature programming and equipped with a wide-bore wall coated open tubular column and a flame-ionization detector is used in the following procedure.
Standard solution: Prepare a solution, in organic-free water, containing, in each mL. 12.0 µg of methylene chloride 7.6 µg of 1,4-dioxane, 1.6µg of trichloroethylene, and 1.2µg of chloroform.
Test solution: Dissolve in organic-free water, and accurately weighed portion of the material to be tested to obtain a final solution having a known concentration of about 20 mg of the bulk pharmaceutical chemical per ml.
Chromatographic Conditions:
Column: A 0.53mm x 30-m fused-silica analytical column coated with a 5µm chemically cross-linked G27 stationary phase, and a 0.53mm x 5-m silica guard column deactivated with phenyl methyl siloxane.

Detector
Flame ionization detector
Carrier gas
Helium
Carrier flow
35 cm/sec
Column Int. Temp
35°C for 5 minutes
Heating rate-I
8°C/minute
Column Temp.
175°C
Heating Rate-II
35°C/minute
Column Temp.
260°C for 16 minutes.
Injector temp.
70°C
Injection volume
1ml
Detector temp
260°C

Inject the Standard Solution, and record the peak responses as directed for Procedure a suitable system is one that yields chromatograms in which all of the components in the Standard Solution are resolved, the resolution, R,   between any two components is not less than 1.0, and the relative standard deviation of the individual peak responses from replicate injections is not more than 15%
Procedure: Separately inject equal volumes of the Standard Solution and the Test Solution into the chromatograph, record the chromatograms, and measure the peak responses.
Identify, based on retention time, any peaks present in the chromatogram of the Test Solution. The identity and peak response in the chromatogram may be established as being from any of the organic volatile impurities listed in Table 1 or from some other volatile impurity eluting with a comparable retention time by mass spectrometric relative abundance methods or by the use of a second validated column containing a different station phase.

18. Assay
Limit: 98.5 % - 100.5 %.
Reagent required
1M Hydrochloric acid
1M Sodium Hydroxide
Procedure
Dissolve 0.500 g in 25.0 ml of 1 M hydrochloric acid. Titrate with 1 M sodium hydroxide, using methyl orange solution as indicator. 1 ml of 1 M hydrochloric acid is equivalent to 36.95 mg of Li2CO3.
Calculation:

                                                   V x M x F x 100                
 % Assay on dried basis. = -----------------------                                                                  
                                                         1 x W            
Where:                                            
V = Consumed volume of 1 M Hydrochloric Acid
M = Molarity of 1 M Hydrochloric Acid
F = Factor
W = Weight of substance



Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
.moc.enilediugamrahp@ofni :liamE Need Help: Ask Question

Click Here

No comments:

Post a Comment