Common Pharmacopeial Calculations

in USP Monographs

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

Common Pharmacopeial Calculations

in USP Monographs

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

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

Miscellaneous tests : loss on drying , loss on ignition Miscellaneous tests : loss on drying , loss on ignition AssaysAssays Related compoundsRelated compounds (chromatographic purity)(chromatographic purity)

Miscellaneous tests : loss on drying , loss on ignitionMiscellaneous 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

AssayAssay

Assay as is

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

Assay dried basis LOD

anhydrous basis waterAssay 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 ResultCommon Calculation for Determination of the Assay Result

Chromatography : Chromatography : HPLC, GCHPLC, GC

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

Spectroscopy and other methodsSpectroscopy and other methods

IR , UV , polarography

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

Determination of equivalence factor in titration-based assay

A + A + BB productsproducts

AcidAcid--base titration base titration RedoxRedox titrationtitration )) Electron transfer

TitrationTitration

Direct titrationDirect titration

Residue or Back titrationResidue or Back titration

TitrationTitration

Direct titrationDirect 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 titrationResidue 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 1. Present all termsterms

2. Its origin should be clearly explained 2. Its origin should be clearly explained

3. Dilution factor3. Dilution factor

4. Including the RRF and RRT in the monograph4. Including the RRF and RRT in the monograph

5. Change 1 5. Change 1 --4 as early as possible4 as early as possible

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

7. Create the new chapter for clarification of the 7. Create the new chapter for clarification of the calculationcalculation

THANK for your attentionTHANK for your attention

DISCUSSIONDISCUSSION

SUGGESTION SUGGESTION

QUESTION ? ? ? ?QUESTION ? ? ? ?