Friday, December 30, 2011


Differece between water content and loss on drying (LOD)   RAJA PATEL

A lot of pharma professionals have the confusion regarding the concept of water contentand loss on drying. Both have considerable difference to understand.

Water content is determined by the Karl Fischer titration method and it consists of only water i.e moisture content. The results does not contain other volatile matter except the water.

Loss on drying (LOD) is determined by heating the sample bellow its melting point in an oven and it includes all volatile matter including water content and solvents.

Loss on Drying is an unspecific analytical technique removing not only water but all other volatile impurities like alcohol etc. from a sample.
The degree of drying is dependent on,
Temperature
Drying time
LOD or total moisture content of Pharmaceutical products can include both bound (e.g. water of hydration) & free water.
In cases there are additional traces of other volatile impurities present , like alcohol ; LOD may be higher than water content.
In other cases , LOD may be lower than water content, as bound crystal water may not be removed by heating.
% LOD = % Water content - % water molecule in the API
The Loss on Drying Test is designed to measure the amount of water and volatile matters in a sample when the sample is dried under specified conditions. e.g 105°C, 3 hours.
The nature of the drug substance that is to be weighed and used in compounding a prescription must be known exactly. If the substance is a hydrate, its anhydrous equivalent weight may need to be calculated. On the other hand, if there is adsorbed moisture present that is either specified on a certificate of analysis or that is determined in the pharmacy immediately before the drug substance is used by the procedure under Loss on Drying, this information must be used when calculating the amount of drug substance that is to be weighed in order to determine the exact amount of anhydrous drug substance required.

Calibration of UV / Visible spectrophotometer


Calibration of UV / Visible spectrophotometer


OBJECTIVE:                                                                                                                      
To provide a procedure for calibration of UV / Visible spectrophotometer.
SCOPE: 
Applicable to the Spectrophotometer in Quality Control Department.
Model    : UV-1700, Pharmaspec.
Manufacturer : Shimadzu Corporation.
RESPONSIBILITY:
Chemist.
PROCEDURE:
Ensure that the connections of the instrument are proper.
Control of Absorbance
Potassium dichromate Solution :
Dry a quantity of potassium dichromate by heating to constant weight at 130°C. Weigh & transfer accurately a quantity not less than 57.0 mg & not more than 63.0 mg to 1000 ml volumetric flask.   Dissolve & dilute in sufficient 0.005M H2SO4 to produce 1000 ml.
Measure the absorbance of potassium dichromate solution at the wavelengths given below.
Calculate value of A (1% 1cm) for each wavelength.
A (1% 1cm) = Absorbance X 10000 / Weight of Potassium dichromate in mg.
Acceptance criteria


Wavelengths (nm)
A [1% 1cm]
Limit
235.0
124.5
122.9 - 126.2
257.0
144.0
142.8 - 145.7
313.0
48.6
47.0 - 50.3
350.0
106.6
105.6 - 108.2




Stringent limits are adopted from IP & BP for acceptance criteria
Resolution power
Record the spectrum of a 0.02% v/v solution of toluene in hexane in the range of 260 nm to 420 nm (before use check the hexane for transmittance, using water as a blank between 260nm to 420nm & use only if transmittance is not less than 97%).
Acceptance criteria:
The ratio of the absorbance at the maximum at about 269nm to that at the minimum at about 266nm is not less than 1.5.
Limit of Stray Light
Prepare a 1.2 % w/v solution of Potassium chloride in water.
Measure absorbance of the above solution at  198.0,199.0,200.0,201.0,202.0 nm using water as blank.
Acceptance criteria:
Absorbance is greater than 2.
Wavelength accuracy, Resolution & Baseline flatness (inbuilt test)
Attach printer directly to the instrument (instead of computer).
Go to Þ MODE press F3 key i.e. Maintenance.
Press ‘1’.
Press Start/Stop key.
After screen changes, ensure that nothing is kept in the optical path & press the Start/Stop key again.
Prints will come after all the three tests are over.
Acceptance criteria:
For wave length accuracy : at 656.1 ± 0.3 nm & at 486.0 ± 0.3 nm.
Resolution: 1.0 nm or less.
Baseline flatness: ± 0.002Abs.
Frequency

Once in a month.

Maintenance / Repairs
When the instrument does not comply with the requirement / tolerance range specified above, the instrument should be labeled “OUT OF CALIBRATION” and should be repaired / serviced.
After repair / maintenance, calibrate the instrument.

REFERENCE

Indian Pharmacopoeia
British Pharmacopoeia
Instruction manual of UV-1700.

CALIBRATION REPORT OF UV / VISIBLE SPECTROPHOTOMETER

Page 1 of 2
SOP Reference –
Date -

Instrument No. – EH/QCD/
Frequency
: Once in a month
Make –

Model –

1.
Control of Absorbance:
Potassium dichromate solution :
Gross Wt. :  ………………….                                 Balance : EH/QCD/
Tare Wt. :  ………………….
Net Wt.    : ………………….                                        ………..           ml with 0.005M sulphuric acid.
Dissolve and dilute 57.0 to 63.0 mg of potassium dichromate in sufficient 0.005M sulphuric acid to produce 1000.0 ml.

Wavelength (nm)
Absorbance
A (1%, 1cm)
Tolerance

235.0

 

 

122.9 to 126.2


257.0

 

 

142.8 to 145.7


313.0


47.0 to 50.3

350.0


105.6 to 108.2

Calculation :

             1%                    Absorbance  x 10000

          A1 cm    = -------------------------------------------------------

                          Weight of potassium dichromate in mg
Remark : Satisfactory / Not satisfactory.
Performed by :
Date :
Checked by :
Date :
2.
Resolution power :
0.02% v/v toluene in hexane : 
             ……….ml   ® 100.0 ml with hexane  / ………  ml   ® 100.0 ml with hexane
Absorbance at 269 nm = ……………
Absorbance at 266 nm = ……………
                          Absorbance at 269 nm
                Ratio = ---------------------------------- =    ---------------- =
                          Absorbance at 266 nm                             
  (Limit : Not less than 1.5)
Remark : Satisfactory / Not satisfactory.
Performed by :                                                                 Checked by:
Date :                                                                                Date           : 

CALIBRATION REPORT OF UV / VISIBLE SPECTROPHOTOMETER

Page 2 of 2
3.
Limit of stray light:
Potassium chloride solution
Gross Wt.                :  ………………….                                  Balance : EH/QCD/                           
Tare Wt. :  ………………….
Net Wt.    : ………………….                          ……………. ml with water.
Dissolve and dilute accurately 1.2 g potassium chloride  in sufficient water to produce 100.0 ml.

Sr. No.
Wavelength (nm)
Absorbance
Tolerance

1
198.0

Absorbance is greater than 2

2
199.0


3
200.0


4
201.0


5
202.0


Remark : Satisfactory / Not satisfactory.
Performed by :
Date :
Checked by :
Date :
4.
 Wavelength accuracy (In built test)
Sr. No.
Wavelength Standard (nm)
Wavelength Observed (nm)
Difference
Limit (nm)
1
656.1


+ 0.3
2
486.0


+ 0.3
Remark : Satisfactory / Not satisfactory.
Performed by :                                                                 Checked by:
Date :                                                                                Date           : 
5.
Resolution (In built test)
Sr. No.
Limit
Observation
1
1.0 nm or less
nm
Remark : Satisfactory / Not satisfactory.
Performed by :                                                                 Checked by:
Date :                                                                                Date           : 
6.
Baseline flatness (In built test)
Sr. No.
Limit
Observation
1
± 0.002 Absorbance

Remark : Satisfactory / Not satisfactory.
Performed by :                                                                 Checked by:
Date :                                                                                Date           : 

Conclusion : Instrument working is Satisfactory / Not satisfactory.

Next calibration due on :
















Performed by :
Date :
Checked by :
Date :