ZIPRASIDONE HYDROCHLORIDE MONOHYDRATE METHOD OF ANALYSIS SOP


1.0  OBJECTIVE:
To lay down a procedure for the active raw material of the Ziprasidone hydrochloride monohydrate from the Pharmacopoeial specifications.
2.0  SCOPE:
This SOP shall be applicable in Q.C laboratory.
3.0  RESPONSIBILITY:
3.1  Q.C Analyst.
4.0  ACCOUNTABILITY:
4.1  Q.C Manager.
5.0  PROCEDURE:
5.1  Characters:
5.1.1        Appearance:
5.1.1.1  White or slightly pink powder.
5.1.2        Solubility:
5.1.2.1  Material and equipment:
5.1.2.1.1        Glassware (3 test tubes, 1 spatula).
5.1.2.1.2        Methanol.
5.1.2.1.3        Methylene chloride.
5.1.2.1.4        Purified water.
5.1.2.2  Sample:
5.1.2.2.1        Small quantity.
5.1.2.3  Method:
5.1.2.3.1        Take 3 test tubes and add small quantity of sample for testing solubility according to B.P specifications.
5.1.2.3.2        Add purified water in test tube 1 and observe.
5.1.2.3.3        Add methanol in test tube 2 and observe.
5.1.2.3.4        Add methylene chloride in test tube 3 and observe.
5.1.2.4  Observations:
5.1.2.4.1        The sample in test tube 1 containing with purified water is practically insoluble.
5.1.2.4.2        The sample in test tube 2 & 3 containing with methanol and methylene chloride are slightly soluble.
5.2  Identification tests:
5.2.1        Chlorides test:
5.2.1.1  Material and equipment:
5.2.1.1.1        Glassware (according to requirement).
5.2.1.1.2        Centrifuge machine.
5.2.1.1.3        Dilute nitric acid.
5.2.1.1.4        Purified water (q.s).
5.2.1.1.5        0.4ml of Silver nitrate R1.
5.2.1.1.6        1.5ml of ammonia.
5.2.1.2  Sample:
5.2.1.2.1        30.0mg.
5.2.1.3  Method:
5.2.1.3.1        Take a test tube add in it 2.0ml of water with the help of pipette.
5.2.1.3.2        Suspend 30.0mg of sample in it.
5.2.1.3.3        Acidify with 0.15ml of dilute nitric acid.
5.2.1.3.4        Filter it by using filtration apparatus.
5.2.1.3.5        Take 2.0ml of the above obtained filtrate in test tube.
5.2.1.3.6        And add 0.4ml of silver nitrate R1.
5.2.1.3.7        Shake and allow it to stand.
5.2.1.3.8        A curdled, white ppt is formed.
5.2.1.3.9        Centrifuge it in centrifugation machine, according to SOP.
5.2.1.3.10    The obtained ppt is wash with 3 quantities, each of 1ml, of water.
5.2.1.3.11    Carry out this operation rapidly is subdued light, degrading the fact that the supernatant solution may not become perfectly clear.
5.2.1.3.12    Suspend the precipitate in 2.0ml of water and add 1.5ml of ammonia.
5.2.1.4  Observations:
5.2.1.4.1        The precipitate dissolves easily with the possible exception of a few large particles which dissolves slowly.
5.3  Assay:
5.3.1        Apparatus:
5.3.1.1  HPLC apparatus.
5.3.1.2  Glassware (according to the requirement).
5.3.2        Material and reagents:
5.3.2.1  Purified water.
5.3.2.2  Methanol.
5.3.2.3  Ziprasidone hydrochloride monohydrate CRS.
5.3.2.4  6.8g/L solution of potassium dihydrogen phosphate R.
5.3.2.5  Phosphoric acid R.
5.3.3        Sample:
5.3.3.1  23.0mg.
5.3.4        Solvent mixture:
5.3.4.1  Purified water R, methanol R (40:60 v/v)
5.3.5        Test solution:
5.3.5.1  Take a beaker of 100.0ml and add 23.0mg of the substance to be examined in it.
5.3.5.2  Add in sufficient quantity of solvent mixture and dissolved it by using magnetic stirrer i.e. SOP.
5.3.5.3  And dilute it to 100.0ml with the solvent mixture.
5.3.6        Reference solutions:
5.3.6.1  Take a beaker of 100.0ml and add 23.0mg of Ziprasidone hydrochloride monohydrate CRS in it.
5.3.6.2  Add in sufficient quantity of solvent mixture and dissolved it by using magnetic stirrer i.e. SOP.
5.3.6.3  And dilute it to 100.0ml with the solvent mixture.
5.3.7        Column:
5.3.7.1  Size:
5.3.7.1.1        Length=0.15m,
5.3.7.1.2        θ=4.6mm.
5.3.7.2  Stationary phase:
5.3.7.2.1        Spherical octylsilyl silica gel for chromatography R (5μm).
5.3.7.3  Temperature:
5.3.7.3.1        40o.
5.3.8        Mobile phase:
5.3.8.1  Mix 40 volumes of methanol R and 60 volumes of a 6.8g/L solution of potassium dihydrogen phosphate R adjusted to pH 3.0 with phosphoric acid R.
5.3.9        Flow rate:
5.3.9.1  1.5ml/min.
5.3.10    Detection:
5.3.10.1 Spectrophotometer at 229nm.
5.3.11    Injection:
5.3.11.1 20μL.
5.3.12    Run time:
5.3.12.1 Twice the retention time of Ziprasidone.
5.3.13    Retention time:
5.3.13.1 Ziprasidone= about 7 min.
5.3.14    System suitability: reference solution:
5.3.14.1    Symmetry factor: Maximum 2.0 for the peak due to Ziprasidone.
5.3.15    Method of analysis:
5.3.15.1    Carry out the test protected from light and prepare the solutions immediately before use.
5.3.15.2    Firstly prepare the test solution, reference solution and mobile phase according to the requirements.
5.3.15.3    The solutions must be free from solid particles.
5.3.15.4    Prepare the apparatus.
5.3.15.5    The mobile phase solvent mixtures must be de-aerated prior to use either by boiling or by applying a partial vacuum to the solvent reservoir.
5.3.15.6    Equilibrate the column with the prescribed mobile phase, flow rate and at temperature specified until a suitable baseline is achieved.
5.3.15.7    Test solution of the mixture to be separated is now introduced into the mobile phase with the help of an injector just before entering the separating column.
5.3.15.8    As the eluate leaves the column it enters a detector, where it is continuously monitored at the specified λ.
5.3.15.9    The electrical signal obtained from detector is amplified and routes to recorder which record the developed chromatogram.
5.3.15.10Calculate the percentage content of Ziprasidone hydrochloride monohydrate (C21H22Cl2N4OS) from the declared content of Ziprasidone hydrochloride monohydrate CRS.
5.3.16    Observations:
5.3.16.1    98.0% to 102.0% (anhydrous substance).
6.0  REVISION LOG:
Revision No.
Effective Date
Reason
00

New SOP

7.0  REFERENCES:
7.1  The British Pharmacopoeia. Vol II., Official Monograph / Ziprasidone hydrochloride monohydrate: 2015, pp. 1209-1211.
7.2  The British Pharmacopoeia. Vol V., Official Monograph /Qualitative Reactions and Tests: 2015, pp. 266-270.
7.3  USP38NF33 Volume-1 Official Monograph/ Chromatography: 2015, pp.: 424-434.
8.0  ANNEXURES:
Annexure 1: Observations and calculations of HPLC method.


Annexure: 1
Observations and calculations of HPLC method
Analysis on HPLC
Instrument: ___________________                                           Date: _________________
Model: ___________________
Column size:
Length=
θ=
Stationary phase:

Temperature:

Mobile phase:

Flow rate:

Injection size:

Detector:

Wavelength:
λ=

Sample solution: _______________________
Reference standard solution: ______________
Impurities: ____________________________
(calculate each component calculation separately)
OBSERVATIONS:
Attach chromatogram.


CALCULATIONS:
1.      Retention time:                                                                                n= no. of peak
Retention time of unretained peak (tm)= _____________
No. of peaks
Retention time of peak of interest
(tr)n
Height of peak of interest
(h)n
Width of peak of interest
(w)n
Area of peak of interest
A=1/2(h x w)




















2.      Retention volume:
Flow rate= _______________ml/min.
No. of peaks
Retention time of peak of interest
(tr)n
Retention volume = retention time x flow rate












3.      Retention factor:
Retention time of unretained peak (tm)= _____________
No. of peaks
Retention time of peak of interest
(tr)n
Retention factor of a component
k= (tr-tm)/tm













4.      Separation factor (α):
No. of peaks
Retention factor of a component
(kn)
Relative retention of two adjacent peaks
α = k2/k1












5.      Resolution:
Retention time of unretained peak (tm)= _____________
No. of peaks
Retention time of peak of interest
(tr)n
Width of peak of interest
(w)n
Resolution
Rs = 2 (tr2-tr1)
        (w1-w2)
















6.      Efficiency:
No. of peaks or components
Retention time of peak of interest
(tr)n
Width of peak of interest
(w)n
Efficiency
(No. of theoretical plates)
N= 16 (tr/w)2


















7.      Height equivalent to a theoretical plate (HETP):
Length of column = ________________________
No. of peaks or components
No. of theoretical plates
(N)
Height equivalent to a theoretical plate HETP = L/N












8.      Symmetry factor (tailing factor):
No. of peaks or components
Distance from the peak max. to leading edge of the peak
(f)
Width w
Symmetry factor
At 5%
At 10%
As = w5%
       2f
As = w10%
       2f
























9.      Response factor & Relative response factor:
Conc. (mg/ml)= ___________________
No. of peak
Peak area
Response factor = (peak area/conc.)
Relative response factor = (response factor of impurity/response factor of API)

















10.  Relative standard deviation (%RSD):
Use formula of relative standard deviation where it is required i.e.,
pic
11.  Percentage of content:
Percentage content = (rU/rS) x (CS/CU) x 100.
rU= peak response of substance from the sample solution.
rS= peak response of substance from the standard solution.
CS= concentration of substance in the standard solution (mg/mL).
CU= concentration of substance in the sample solution (mg/mL).











RESULTS:
________________________________________________________________________________________________________________________________________________


9.0  ABBREVIATIONS:
Abbreviation
Expanded Form
SOP
Standard operating procedure
&
And
No.
Number  
Ltd.
Limited
QCA
Quality control active ingredient
F
Format
Q.C
Quality control
Vol
Volume
g
Grams
ml
Milliliter
oC
Degree centigrade
mg
Milligram
M
Molar
%
Percentage
R
Reagent
μm
Micron/ micrometer
g/L
Gram per liter
CRS
Chemical reference solution
m
Meter
θ
Theta
mm
Millimeter
ml/min
Milliliter per minute
nm
Nanometer
μL
Microliter
Min
Minute
λ
Lamda


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