PROCAINE PENICILLIN ( I.P.

C13H20N2O2,C16H18N2O4S,H2O

Procaine Penicillin is 2-diethylaminoethyl 4-amino- benzoate (6R)-6-(2-

phenylacetamido) penicillanate monohydrate.

Molecular Weight : 588.72

Category: Antibacterial.

Dose: By intramuscular injection, 300 to 900 mg daily (300 mg of Procaine Penicillin is

approximately equivalent to 200 mg of benzylpenicillin).

Description: White, crystalline powder.

Solubility: Slightly soluble in water; sparingly soluble in ethanol (95%).

Storage: Store in tightly-closed containers in a cool, dry place. If the material is

intended for use in the manufacture of injectable preparations, the container should be
sterile and sealed so as to exclude micro-organisms.

STANDARDS :
Procaine Penicillin contains not less than 96.0 per cent and not more than 102.0 per
cent of penicillins, calculated as C13H20N2O2,C16H18N2O4S, and not less than 39.0
per cent and not more than 42.0 per cent of procaine, C 13H20N2O2, both calculated
with reference to the anhydrous substance.

Identification Test A may be omitted if tests B, C and D are carried out. Tests B, C and
D may be omitted if test A is carried out.
A: The infra-red absorption spectrum, Appendix 5.4, is concordant with the reference
spectrum of procaine penicillin or with the spectrum obtained from procaine penicillin
RS.

B: Complies with the test for identification of penicillins, Appendix 3.1.

C: Gives reaction B of penicillins and cephalosporins, Appendix 3.1.

D: A turbid solution of 0.1 g in 2 ml of 2M hydrochloric acid gives the reaction of primary

aromatic amines, Appendix 3.1.

pH: Between 5.0 and 7.5, determined in a solution prepared by shaking 50 mg in

sufficient carbon dioxide-free water to produce 15 ml until dissolution is complete,
Appendix 8.11.

Specific optical rotation: Between +165o and +180o, determined in a solution

prepared by dissolving 0.25 g in sufficient of a mixture of 3 volumes of acetone and 2
volumes of water to produce 25 ml, Appendix 8.9.

Water: Between 2.8 and 4.2% w/w, determined on 0.5 g, Appendix 3.24.

Pyrogens: Complies with the test for pyrogens, Appendix 2.6, using per kg of the
rabbit's weight 0.5 ml of a solution in sodium chloride injection containing 5 mg per ml.

Procaine Penicillin intended for use in the manufacture of injectable preparations

without a further sterilisation procedure complies with the following additional
requirement.

Sterility: Complies with the tests for sterility, Appendix 9.5.

Assay: For penicillins — Weigh accurately about 70 mg, dissolve in 1 ml of methanol,

add 5 ml of water and 5 ml of 1M sodium hydroxide and allow to stand for 15 minutes.
Add 5 ml of1M nitric acid, 20 ml of acetate buffer pH 4.6 and 20 ml of water. Titrate at
35° to 40° with 0.02M mercuric nitrate. Determine the end-point potentiometrically using
a mercury or platinum indicator electrode and a mercury-mercuric sulphate reference
electrode; titrate slowly so that the titration takes about 15 minutes and ignore any
preliminary inflection on the titration curve. Each ml of 0.02M mercuric nitrate is
equivalent to 0.011414 g of total penicillins, calculated as
C13H20N2O2,C16H18N2O4S
Amendment 1. Weigh accurately about 0.25 g, dissolve in 25 ml of methanol and add
25 ml of acetate buffer pH 4.6. Titrate immediately at room temperature with 0.02M
mercuric nitrate determining the end-point as above. Each ml of 0.02M mercuric nitrate
is equivalent to 0.011414 g of degradation products, calculated as
C13H20N2O2,C16H18N2O4S.Subtract the percentage of degradation products found
from the percentage of total penicillins found; the difference is the content of penicillins,
calculated as C13H20N2O2,C16H18N2O4S.

For procaine — Weigh accurately about 0.1 g, dissolve in sufficient methanol to produce
100.0 ml, dilute 5.0 ml to 250.0 ml with water and measure the absorbance of the
resulting solution at the maximum at about 290 nm, Appendix 5.5. Calculate the content
of C13H20N2O2 taking 777 as the value of A(1%, 1 cm) at the maximum at about 290
nm.

Procaine Penicillin intended for use in the manufacture of injectable preparations

without a further procedure for the removal of pyrogens complies with the following
additional requirement.

Marketed Preparations :

Preparations :Penicillin G Benzathine and Penicillin G Procaine Injectable

Suspension;Penicillin G Procaine for Injectable Suspension; Penicillin G Procaine
Injectable Suspension

Comparison between IP and USP :

Parameter IP
Storage Tightly-closed containers
Bacterial endotoxins Not defined
Assay Potentiometric method
Labelling The label states contents are
Apyrogenic and/or sterile
Identification IR Spectrum
Limits Procaine Penicillin contains
not less than 96.0 per cent
and not more than 102.0
per cent of penicillins,
USP
Containers for Sterile Solids
NMT 0.01 USP Endotoxin
Unit per 100 Penicillin G
Units
Iodometric Method
Label states it is sterile
TLC method
Penicillin G Procaine has a
potency of not less than
900 Penicillin G Units
and not more than 1050
Penicillin G Units per mg

Note : Procaine penicillin is not official in British Pharmacopoeia (B.P.)