ASSAY OF CLOPIDOGREL BISULPHATE BY HPLC METHOD

Preparation of phosphate buffer solution : Dissolve 2.72gms of monobasic potassium phosphate in about 500ml of water and dilute to 1000ml with same solvent. Adjust pH to 6.0 ± 0.1 with KOH.

Mobile Phase :  Prepare a filtered and degassed mixture of Phosphate Buffer and acetonitrile (35:65) .Make adjustment if necessary.

Standard Preparation : Dissolve 50mg 0f Clopidogrel Bisulphate Working Standard in methanol, sonicate and make volume to 50ml with methanol.Dilute 5ml of solution to 50ml with mobile phase (conc.0.1mg/ml). Filter the solution with 0.22µm before injection.

Assay Preparation : Crush finely 20 tablets into powder and weigh an amount of powder containg 100mg of Clopidogrel Bisulphate in a 100ml volumetric flask . Dissolve the content with methanol, sonicate and dilute with methanol to volume and mix, filter. Pipette 5ml of this solution to a 50ml volumetric flask, dilute with mobile phase to volume and mix.

Chromatographic System :

Column                  : 4.6mm x 25cm column that contains packing L1

Flow rate              : 1.5ml /min

Wavelength          : 265nm

Temperature                  : Ambient

Injection volume   : 20µL

The relative standard deviation (RSD) for replicate injections determined from Clopidogrel Bisulphate is not more than 1.0% .

Procedure :

Seperately inject equal volumes (about 10µL) of the standard preparation and the assay preparation into the chromatograph ,record the chromatograms, and measure the areas for all peaks . Calculate the quantity in mg of C₁₆H₁₆ClN0₂S.H₂S0₄ in

The portion of the tablet taken by the formula :

                                          Peak area of sample     Wt.of sample

% of Clopidogrel Bisulphate :------------------------X  --------------------X Potency of WS

                                           Peak of standard        Wt.of standard      

Where :  WS is the Working Standard .

Assay of Atorvastatin (UV-VIS) Spectrophotometric Method

Preparation of Standard Solution :  Take 10mg. of Atorvastatin Calcium Trihydrade in a 100ml volumetric flask, add 50ml of Methanol and sonicate , dilute to volume with the same solvent. Transfer 5ml of this solution in a 50ml Volumetric flask and dilute to volume with methanol.

Preparation of Sample Solution : Crush 20 tablets finely and weigh an amount of powder tablet containing 10mg of Atotvastatin Calcium Trihydrade in a 100ml Volumetric Flask ,add 50ml Methanol and sonicate , dilute to Volume with methanol and filter. Transfer 5ml of the filtrate in a 50ml volumetric flask and make volume with methanol.

Measure the absorbance of the resulting solutionat the maximum wavelength at 247nm,using a methanol as blank.

Calculation :

                        

                                Absorbance of sample x weight of standard

% of Atorvastatin = …………………………………………… X Potency of Standard                   

                                 Absorbance of Std.x Weght of sample x 1.084                                                                          

Sampling of Raw Materials

1.0      PURPOSE:  To ensure the smooth sampling of raw materials. It is important that the Sampling is done in an appropriate manner so that a representative sample is taken. 2.0      SCOPE:  Any materials related to manufacturing which is entering the warehouse, Must be sampled properly. 3.0      DEFINITIONS :  Nil 4.0      RESPONSIBILITY: QC officer 5.0      PROCEDURES: 5.1      After receipt of the material in the warehouse the store officer will send an Advice note to the QC department for sampling the material. The advice note Will contain in following information:             5.1.1        Name of the material 5.1.2        Name of the product 5.1.3        Country of origin 5.1.4        Control number of the product 5.1.5        Date of manufacturer 5.1.6        No. of containers received 5.1.7        Description of the containers received 5.1.8        Pack size of the containers.                    Sampling should be done in the following manner:                         5.2.1  Up to three containers        -       from one container                         5.2.2  From 4 to 5 containers       -       from 2 containers                         5.2.3  From 6 to 15 containers     -       from 3 containers                         5.2.4  From 16 to above               -       from every 5th container

Sample should be collected in inert container so that they do not react with the sample. For powdered materials samples should be taken with suitable sampling scoops made up of inert materials. For liquid this should be taken with glass sampling tubes. Suitable siphons may be used in case of sampling thick liquids. Amounts of sample taken should be at least twice the amount required for complete test.

Oral Liquid Manufacturing Flow Chart

 01.   Weighing &

    Mixing

       

02. Capsule

       Filling

03. Polishing

04.     Blistering

05. Inner Cartooning

06.    Master

Cartooning

. 

Disposal of Microbiological waste material

1.0        Purpose: To ensure a system adopted by Pharmaceuticals Limited for disposal of microbiological waste materials. 2.0        Scope: This SOP applies to the  waste materials generated in Pharmaceuticals Limited from microbiological work. 3.0        Definition: Nil. 4.0        Responsibility: Q.C Officer 5.0        Procedures: 5.1        Microbiological waste generated in the microbiological lab is heated under 15lb pressure at 1210C for half an hour in an autoclave machine. 5.2        After heating the autoclave machine is allowed to cool down. 5.3        Waste material is taken to a sink with water tap. Water tap is turned on & the waste material is allowed to drain off with sufficient water.

Calibration of UV- VIS Detector for HPLC

1.0      PURPOSE:  To ensure smooth functioning of HPLC Machine. 2.0      SCOPE  :  The SOP applies to the calibration of UV-VIS detector of Shimadzu                          Company model No. SPD-10A vp. 3.0   DEFINITION:    Nil. 4.0 RESPONSBILITY:  Quality Control officer. 5.0  PROCEDURES: 5.1      Press & hold down the “shift” key & turn the power switch on. 5.2      Press the “func” key until lamp is displayed. 5.3      Press  “1”, then enter. 5.4      Press “func” until “Wave check” is displayed. 5.5      Press “enter”. The wavelength accuracy check is run automatically. CHECK GOOD should appear on the screen when the test ends.

Calibration of Spectrophotometer

1.0   PURPOSE:   To ensure smooth functioning of Spectrophotometer. 2.0   SCOPE   :   The SOP applies to the calibration of Spectrophotometer of Shimadzu                             Company model No. UV-1201 3.0   DEFINITION:  Nil. 4.0  RESPONSIBILITY :  QC officer. 5.0  PROCEDURE: 5.1  Switch on the machine & wait for auto calibration . 5.2  After auto calibration check the absorbance of potassium Dichromate Solution VS at the wavelengths indicated in the following table which gives for each Wavelength the exact value of A (1% 1cm) & the permitted limits. The tolerance of absorbance is ± 0.01           Wavelength (nm)                     A(1% 1cm)                     Maximum Tolerance                     235                        -                124.5           -                  122.9 – 126.2                  257                        -                 144.0           -                  142.4 – 145.2                  315                        -                 48.6            -                    47.0 – 50.3                  350                        -                 106.6           -                   104.9 – 108.2