The United States Pharmacopia has been recognized for years as an authoritative compendium on drug standards. In recent years, it has paid increasing attention
to "microbial purity," i.e., freedom from and control of objectionable bacteria and fungi and included writings on the theory and practice of antimicrobial
agents. A reading of Chapter ‹1072› in current USP 29 (Antiseptics and Disinfectants), however, reveals inaccuracies in organic chemistry, proper selection of agents, and ingredient
concentrations. Although these errors or inaccuracies do not affect drug purity, they are evidence of a revision process that
fails to circulate early drafts to the right people.
Item No. 1:
The remarks following Table 3 in Chapter ‹1072› discuss the ionization of weak acids such as phenol and acetic acid, both
rarely used in the pharmaceutical plant as microbicides. It is correctly stated that phenol is more active in killing microorganisms
below pH 7.0 because it is mostly un-ionized. The same common ion effect would be obtained for acetic acid as well, but the
author reverses the equation and states that "acetic acid will be more effective at a pH below 4.0 where it is ionized" (1).
The equation is
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The pKa of acetic acid is 4.55. By the rule of 2-above-2-below, at pH 6.55 the acid is highly ionized and at pH 2.55 it is
practically all un-ionized. At pH 4.0, as cited by the author, it cannot be said to be "ionized;" as a matter of fact, about
90% is just the opposite. Thus, fungi and a few aciduric bacteria will be killed rapidly because the molecule exists mainly
as HOAc un-ionized. This pH-dependant lethality is, we believe, what the author tried to convey. But if what is said is not
clear, it should not be said.
Item No. 2:
Table 2 misspells glutaraldehyde, and Table 4 mistakenly lists glutaraldehyde as an oxidizing agent. Glutaraldehyde exerts its effect by covalent bonding
to amino groups or other susceptible sites on nucleic acids or polypeptide chains. In chemistry, a nucleophile (literally, "nucleus lover") is a reagent that forms a chemical bond to its reaction partner (the electrophile) by donating
both bonding electrons. Its mechanism is the same as formaldehyde but it is less toxic. No manufacturer of this germicide
has ever claimed glutaraldehyde to be an oxidizing agent, like chlorine, nor will any textbook of organic chemistry so state.
A common definition of an oxidizing agent is a substance that gains electrons in a redox chemical reaction.
In this same table, ethylene oxide is listed as an oxidizing agent. For classification purposes, it should be grouped with
formaldehyde and glutaraldehyde. It is an alkylating agent. Alkylating agents increase the size of a molecule, oxidizing agents
generally degrade them.
Item No. 3:
In Table 2, "General Classification of Antiseptics, Disinfectants, and Sporicidal Agents," benzalkonium chloride is listed
at a use concentration of 200 μg/g. This single concentration does not fit any of the standard marketed products now available
that might include this agent. For example, it is too low for use as a disinfectant, for first-aid preparation, or for cosmetic
use (the usual range is 1000–3000 μg/g for these uses) and it is too high to be used as an ophthalmic preservative, for which
the range is 30–100 μg/g.
