Common Pharmacopeial Calculations

in USP Monographs

(Pharmacopeial Forum vol.31(2) [Mar.-Apr. 2005])

Ê Miscellaneous tests : loss on drying , loss on ignition

Ê Assays
Ê Related compounds (chromatographic purity)
Miscellaneous tests : loss on drying , loss on ignition

Loss on drying % LOD

%LOD = [(T-F)/(T-C)] x 100

Loss on ignition % LOI

%LOI = [(T-F)/(T-C)] x 100

 Assay

Assay “ as is ”

Calculation = Q/T x 100 = 495 / 500 x 100 = 99.0%

Assay “ dried basis ” LOD

“anhydrous basis ” water

Assay result = [Q/T/(100-A/100)] x 100

= [295.0/300.0/(100-0.34)/100] x 100 = 98.7%

Assay “ on ignition basis ”

Assay result = [Q/T/(100-A/100)] x 100

= [96.0/99.8/(100-3.54)/100] x 100 = 99.7%

Assay result on previously dried basis

Calculation = Q/T x 100 = 10.7 / 10.5 x 100 = 101.9%

Assay result calculated on the anhydrous and solvent-free basis

Calculation = [Q/T/(100-A-B)/100] x 100

= 26.0 / 25.9/(100-0.183-0.281)/100]x100

= 101.9%
Common Calculation for Determination of the Assay Result

Chromatography : HPLC, GC

50C(ru/rs), DC(ru/rs), (301.39/337.84)(50C)(ru/rs)

Spectroscopy and other methods

IR , UV , polarography

10C(Au/As), P (Ws/Wu) (iu/is)

Determination of equivalence factor in titration-based assay

αA + βB products

Acid-base titration
Redox titration ) Electron transfer

Titration

Direct titration

Residue or Back titration

Titration

Direct titration

Assay result = [(V-B) x N x F x 100]/[TN x W x(100-A)/100] x100

= [(8.5-1.4)x0.11x25.43x100]/[0.1x202x(100-0.42)/100]

= 98.7%

Residue or Back titration

Assay result = [(B-V) x N x F x 100]/[TN x W] x100 =

= [(43.78-15.10)x0.9993x30.05x100]/[1.0x1007.8]

= 99.7%
Related compounds or chromatographic impurity

Impurity in New Drug Substance

- Inorganic impurities
- Residue solvent
- Organic impurities HPLC , GC

)Total peak area : 100(ri/rs)

)Different concentration of the test sample: 100ri/(rs+5ru)

)Using reference standard : 0.1(Cs/Cu)(ru/rs)

)Using relative response factors (RRF) : 100F(Cs/Cu)(ru/rs)

 Recommendations

1. Present all terms

2. Its origin should be clearly explained

3. Dilution factor

4. Including the RRF and RRT in the monograph

5. Change 1 -4 as early as possible

6. Formulas are expressed in the same unit as in the

assay

7. Create the new chapter for clarification of the

calculation
 THANK for your attention

DISCUSSION

SUGGESTION

QUESTION ? ? ? ?