Standard Operating Procedure (SOP) for Finished Product Analysis of Sertraline Hydrochloride by UV and HPLC Method
PURPOSE:
To describe the procedure for analysis at the in-process and finished stage of the Sertraline Hydrochloride Tablet.
SCOPE:
This SAP gives a detailed outline for the finished product analysis of the Sertraline Hydrochloride Tablet and will cover In process testing activities on a physical, chemical & instrumental basis.
RESPONSIBILITY:
QC Analyst is responsible for physical/chemical testing and preparing standard analytical procedures.
It is the responsibility of QC Manager to assist and ensure the Testing Procedure as per SAP and to make certain that this SAP is followed in its entirety, reviewed regularly, and revised as necessary.
REFERENCE:
USP 44, NF 39
MATERIAL AND EQIUPMENT:
- UV Spectrophotometer
- HPLC
- Dissolution apparatus
- Friability apparatus
- Hardness apparatus
- Disintegration Tester
- Vernier Caliper
- Analytical Balance
- Moisture analyzer
- Mortar and pestle
- Spatula
- Filter Paper
- Magnetic Stirrer & Hot Plate
- Sonicator
- Vacuum Pump
- Glassware
- Distilled water
- 0.1 N Hydrochloric acid
- Ammonium Acetate
- Glacial Acetic Acid
- Methanol
PROCEDURE:
FINAL MIX
SOP for Finished Product Analysis of Sertraline Hydrochloride Tablet By UV and HPLC Method
Description:
A white powder.
Procedure: Take 2.0 g of the test sample in a watch glass and observe visually with black background. Check the appearance of color, nature and any visible foreign particles.
Identification:
The spectrum of the sample preparation corresponds to spectrum of the standard preparation as obtained in the assay.
The retention time of the Sertraline as HCl peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
Assay By HPLC:
(Limit: 90%-110%)
Procedure:
Mobile phase: Methanol and 0.1% (v/v) phosphoric acid(1:1)
Standard solution: 0.05 mg/mL of USP Sertraline Hydrochloride RS in Mobile phase
Sample stock solution: 0.5 mg/mL of sertraline free base prepared as follows. Transfer NLT 10 Tablets to a suitable volumetric flask. Dissolve in 0.1% phosphoric acid equivalent to 50% of the flask volume. Sonicate for 15 min with intermittent shaking to disperse the Tablets. Add an amount of methanol equivalent to 40% of the flask volume, and continue to sonicate for an additional 10 min. Cool the solution, and dilute with methanol to volume.
Sample solution: Nominally 0.05 mg/mL of sertraline freebase in Mobile phase from the Sample stock solution. Pass a portion of this solution through a nylon filter of 0.45um or finer pore size, discard the first few mL, and collect the rest of the filtrate.
Chromatographic system
(See Chromatography (621),System Suitability.)
- Mode: LC
- Detector: UV 210 nm
- Column: 4.6-mm x 25-cm; 5-um packing L10
- Column temperature: 30°
- Flow rate: 1.5 mL/min
- Injection volume: 10 µL
- Run time: Twice the retention time of sertraline
System suitability
- Sample: Standard solution
Suitability requirements
- Tailing factor: NMT2.0
- Relative standard deviation: NMT1.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of sertraline free base (C17H17CI2N) in the portion of Tablets taken:
- Result = (Ru/Rs) x (Cs/Cu) x (Mr1/Mr2) x 100
- Ru=peak response from the Sample solution
- Rs =peak response from the Standard solution
- Cs = concentration of USP Sertraline Hydrochloride RS in the Standard solution(mg/mL)
- Cu = nominal concentration of sertraline free base in the Sample solution(mg/mL)
- Mr1 = molecular weight of sertraline, 306.23
- Mr2=molecular weight of sertraline hydrochloride,342.69
- Limit: Sertraline free base: 90%-110%of the labeled amount
Alternate Method By UV
Procedure:
Diluent: Methanol: Water 50 : 50
Standard Solution:
Take 28 mg of Sertraline HCl WS equivalent to 25mg of Sertraline dissolved in diluent and make up the volume to 50mL with diluent. Shake, and sonicate for 5 minutes to facilitate dissolution
Take 5 mL from standard stock solution and make up the volume to 25 mL with diluent.
Sample solution:
Take 5gram of sample grind them to fine powder. Take weight of finally grinded powder equivalent to 50mg of Sertraline and dissolved in diluent and make up the volume to 100 with diluent. Shake by mechanical mean for 10 minutes to disperse and allow any insoluble matter to settle.
Pass a portion of the sample stock solution through a suitable filter of 0.45um pore size.
Transfer the 5 mL of filtrate to a 25 mL volumetric flask make up volume with diluent. Take reading at UV spectrophotometer at 274 nm using diluent as blank.
Calculations:
Sample Absorbance x Standard Concentration x Ave. Weight of Tablet x Potency
Standard Absorbance x Sample Concentration x Label Claim
Limit: Sertraline as HCl: 90%-110%of the labeled amount
Hardness Test & Dimensions:
Perform the hardness test on 10 tablets and take the average. Power on the instrument and regulate zero adjustment and preset the ‘’HARDNESS’’ and “Thickness” mode. Place the tablet on the test plate, begin testing and read the hardness thickness and diameter. Clean the shattered tablet and print out test results, perform the test on 10 tablets and take the average.
Hardness Standard Limit:
Thickness Standard Limit:
Length/Diameter Standard Limit:
Friability Test:
For tablets with a unit mass equal to or less than 650 mg, take a sample of whole tablets corresponding to 6.5 g. For tablets with a unit mass of more than 650 mg, take a sample of 10 whole tablets. The tablets should be carefully dedusted prior to testing. Accurately weigh the tablet sample, and place the tablets in the drum. Rotate the drum 100 times, and remove the tablets. Remove any loose dust from the tablets as before, and accurately weigh. Generally, the test is run once. If obviously cracked, cleaved, or broken tablets are present in the tablet sample after tumbling, the sample fails the test. If the results are doubtful or if the weight loss is greater than the targeted value, the test should be repeated twice and the mean of the three tests determined. A maximum mean weight loss from the three samples of not more than 1.0% is considered acceptable for most products.
% FRIABILITY= W1-W2 x 100/W1
Disintegration Test:
Place the beaker filled with water into the beaker stand inside the bath and. Switch on the instrument, set the temperature at 37ºC± 2º C and wait till the temperature of the beaker reaches to the 37ºC± 2º C. Engage the basket on basket hook put the tablets in 6 tubes individually and place the discs then start the oscillations and timer. Note the disintegration time of all the six tablets.
Note the Disintegration time of 1st tablet to the last tablet.
Disintegration Time: NMT 15 minutes at 370C ± 20C
Acceptance criteria of disintegration for tablets:
If 1 or 2 tablets fail to disintegrate completely repeat the test on 12 additional tablets, not less than 16 of the totals of 18 tablets tested disintegrate completely.
BLISTER STAGE:
Leak Test:
Take 06 blisters of tablet 03 filled and 03 empty. Dip these blisters in the bowl of leak test apparatus containing colored water. Create vacuum 250 mmHg and hold for one minute. Release vacuum and check the penetration of water inside the blisters. All blisters should be free of water.
Dissolution Test:
USP Apparatus: USP Apparatus II Peddle
Medium: Acetate Buffer pH 4.50; 900 mL
Speed: 75 rpm
Time: 30 Minute
Medium Temperature: 37º ± 0.5º
Recommended Sampling Time: Sertraline as HCl: 30 Minute
Diluent: Dissolution medium
Medium (Acetate Buffer pH 4.50): Acetate buffer (3.0 g/L of sodium acetatetrihydrate and 1.6 mL/L of glacial acetic acid; adjust with glacial acetic acid to a pH of 4.5)
Standard stock solution:
0.56 mg/mL of USP Sertraline Hydrochloride RS in Medium. A small volume of methanol, not exceeding 5% of the final volume, may be used to help solubilize sertraline.
Standard solution
For Tablets labeled to contain 50, 100, 150, or 200 mg:
0.056 mg/mL of USP Sertraline Hydrochloride RS in Medium from the Standard stock solution
For Tablets labeled to contain 25 mg:
0.028 mg/mL of USP Sertraline Hydrochloride RS in Medium from the Standard stock solution
Sample solution
Pass a portion of the solution under test through a suitable filter of 0.45-um pore size. Dilute with Medium, if necessary.
Mobile phase: Acetonitrile and 0.1% (v/v)phosphoric acid (1:3)
Chromatographic system
(See Chromatography (621), System Suitability.)
- Mode: LC
- Detector: UV 210 nm
- Column: 4.6-mm x 25-cm; 5-um packing L10
- Column temperature: 40°
- Flow rate: 1.5 ml/min
Injection volume
- For Tablets labeled to contain 50, 100, 150, or 200 mg: 10 uL
- For Tablets labeled to contain 25 mg: 20 uL
System suitability
- Sample: Standard solution
Suitability requirements
- Tailing factor: NMT2.0
- Relative standard deviation: NMT2.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of sertraline free base (C17H17CI2N) dissolved:
- Result = (Ru/Rs) x (Cs/L) x (Mr1/Mr2) x D x V x 100
- Ru=peak response from the Sample solution
- Rs=peak response from the Standard solution
- Cs=concentration of USP Sertraline Hydrochloride RSin the Standard solution(mg/ml)
- L= label claim (mg/Tablet)
- Mr1= molecular weight of sertraline, 306.23
- Mr2= molecular weight of sertraline hydrochloride,342.69
- D= dilution factor for the Sample solution
- V=volume of Medium, 900 ml
Tolerances: NLT 80% (Q) of the labeled amount of sertraline free base (C17H17CI2N) is dissolved.
CONTENT UNIFORMITY TEST: (By weight variation)
Calculation of Acceptance Value (AV):
Limits:
L1= ≤ 15 (For 10 Unit)
L2= ≤ 25 (For 30 Unit)
General Formula = M-x̄ ±ks
Acceptability Constant = (k)
Standard Deviation (SD) = s
Number of Units = (n)
Reference Value = M
Mean of Individual Content = x̄