SC I F. Declaration of Content

This section describes the way in which the content of active substance in a preparation is declared and the method adopted to express the content of the medicinal substances themselves. A proper understanding of such statements is essential to their correct interpretation.

Medicinal substances

1. The purpose of the assay in monographs for medicinal substances, taken in conjunction with the tests for impurities, is to determine the purity of the medicinal substance and the limits are therefore usually stated in terms of the molecular entity (salt, ester, etc.) and calculated with reference to the anhydrous or dried substance as appropriate (depending on whether the monograph includes a test for water or for loss on drying).

2. One advantage of this form of expression in ‘parent’ monographs is that it gives an indication ‘at a glance’ of the purity of the substance. For example (albeit an extreme example) the purity of Amitriptyline Embonate is stated as not less than 98.5% of (C₂₀H₂₃N)₂,C₂₃H₁₆O₆ calculated with reference to the anhydrous substance rather than as not less than 57.9% of C₂₀H₂₃N calculated with reference to the anhydrous substance.

3. The mode of expression chosen for the ‘parent’ monograph in no way circumscribes that which may be used in the monograph for a preparation. There is no reason why the two should be the same and there is frequently good reason why they should be different. In the example of Amitriptyline Embonate, the assay limits for the preparation Amitriptyline Oral Suspension are stated in terms of amitriptyline, C₂₀H₂₃N in the BP 2000.

Formulated preparations

4. The purpose of the assay in monographs for formulated preparations is to determine whether the content of the active ingredient is within acceptable limits of the labelled claim and the limits are therefore of necessity stated in terms of the moiety declared on the label as established by the manufacturer.

5. Every effort is made in the British Pharmacopoeia to achieve internal consistency within monographs, that is, to use the same terms for content statement, assay and label. The British Pharmacopoeia Commission, however, has no means of achieving external (inter-monograph) consistency since, unless it perceives there to be a potentially serious risk, it would not seek to obtain a change in a manufacturer’s established practice. Problems arise when a manufacturer is not consistent or does not state clearly to what the strength refers and, in particular, when different manufacturers of the same preparation express the content in different terms.

6. Ideally in many cases where several salts or hydrated forms of the same drug substance are available, the label and dose (and therefore all monograph statements) should be in terms of the anhydrous free base or acid, that is, the active moiety, in order to facilitate comparison and equivalent dosage.

7. Implementation of such a policy would clearly require that each case should be judged on its merits since there would be instances when, for example, a different salt is considered as a different active moiety or where it would be misleading to suggest that two different forms are therapeutically equivalent. Nevertheless it is strongly recommended that as a general rule for new drug substances, doses and strengths of preparations should be expressed in terms of the active moiety.

8. Meanwhile, for established materials the Pharmacopoeia will continue to reflect current practice. In this respect it should be noted that the labelling requirements of the Pharmacopoeia are not comprehensive. Thus a monograph requirement to state the content of active ingredient in terms of the entire drug substance molecule does not preclude an additional indication of the content expressed in terms of the active moiety where such an indication is considered desirable.