Complexation of Procainamide With Dextrose
Complexation of Procainamide With Dextrose
Complexation of Procainamide With Dextrose
V. DAS GUPTA
Received June 8,1981, from the University of Houston, College of Pharmacy, Department of Pharmaceutics, Houston, TX 77030. Accepted
for publication November 20,1981.
Abstract The percent of procainamide complexed with dextrose was of potency after 24 hr of storage (1).It has been predicted
determined to be directly related to the concentration per mole fraction that procainamide may be forming a reversible association
of dextrose in the solution. The complexation process was reversible and complex with dextrose (2). Procainamide is considered
did not proceed at lower pH (-1.5). The rate of formation of complex was unusually stable towards hydrolysis in the pH range of 2-7
dependent on the initial pH value of the solution and the pH decreased
as the concentration of the complex increased. The increase in the con- (3) even at higher temperatures.
centration of procainamide did not change the equilibrium concentration The separation of procainamide from p -aminobenzoic
of the complex. The addition of sodium chloride or edetate disodium did acid (the major product of degradation) using high-pres-
not alter the rate of formation of the complex or its equilibrium concen- sure liquid chromatography (HPLC) has been reported (2).
tration. The addition of hydrochloric acid prevented the formation of The other product of degradation, diethylethylenediamine,
the complex and on adding hydrochloric acid after the formation of the
complex, procainamide was completely freed. did not absorb light to record a peak in the chromatogram.
An additional peak from the interaction of dextrose and
Keyphrases o Dextrose-complexation of procainamide 0 Procain- I was observed in the chromatogram.
amide-complexation, with dextrose Complexation-procainamide
with dextrose The purpose of this investigation was to study the
complexation of procainamide with dextrose. The study
was conducted using an HPLC method similar to that
Procainamide (I) is often mixed with 0.9% NaCl or 5% previously reported (2) in the literature.
dextrose solution in water. The mixture is usually ad-
ministered by continuous intravenous infusion for the EXPERIMENTAL
treatment of certain cardiovascular diseases.
Procainamide is stable when mixed with sodium chlo- Chemicals and Reagents-All chemicals and reagents were USP,
NF, or American Chemical Society grade and were used as received.
ride solution (1)but in 5%dextrose solution, the stability Procainamide hydrochloride' was used without further purification.
is doubtful (1,2). For example, one such solution lost -12% Apparatus-A high-pressure liquid chromatograph2equipped with
a multiple wavelength detector3,a recordeld, and a digital integratol.5was
used.
Column-A semipolar column6 (30 cm long X 4-mm i.d.) consisting
of a monomolecular layer of cyanopropylsilane permanently bonded to
silica gel was used.
Chromatographic Conditions-The mobile phase was 40% (v/v)
acetonitrile in water containing 0.02 M ammonium acetate (pH -7)7, and
J
0
1
4
\
8
I
MINUTES
I
I
0
I
4
I
8
0 1.5 3.0
DAYS
4.5 6.0
From dextrose 5%in water, Travenol Laboratories,Deerfield,Ill. From sodium complex are reported in Table I. All were prepared using a simple solution
chloride, 0.9%in water, Travenol Laboratories,Deerfield, Ill. From dextrose an- method. The solutions were assayed (see procedure following) and
hydrous, USP, J. T. Baker Chemical Co., Phillipsburg, N.J. transferred to amber-colored bottless and stored a t room temperature
(24 *lo).They were reassayed after appropriate intervals and pH values
the flow rate was 2.0 ml/min. The detector was set a t 280 nm (wavelength were also determined.
of maximum absorption), sensitivity was 0.04, the temperature was Preparation of Assay Solution-All the solutions were diluted with
ambient, and the chart speed was 30.5 cm/hr. water to contain 15.0 pg/ml of I (based on the label claim) and 200.0 pg/ml
Preparation of Solutions-The stock solutions of procainamide of I1 (internal standard).
hydrochloride (1.0 mg/ml) and the internal standard, methapyrilene Assay Procedure-A 20.04 aliquot of the assay solution was injected
hydrochloride (5.0 mg/ml) in water, were prepared daily. A standard into the chromatograph using the described conditions. For comparison,
solution was prepared by transferring a 1.5-ml quantity of the stock so- an identical volume of the standard solution was injected after the assay
lution of I and a 4.0-ml quantity of the stock solution of methapyrilene solution eluted.
hydrochloride (11) to a 100-ml volumetric flask and then diluting with Calculations-The results were calculated using:
water to volume.
All solutions prepared for investigations of procainamide-dextrose Phl X 100 = Percent of the label claim
-
Phs
r Where Ph, is the ratio of the peak heights of procainamide and metha-
pyrilene of the assay solution and Ph, that of the standard solution of
an identical concentration.
t
I I I I I I
0 1 2 3 4 5
OF DEXTROSE
PERCENT
oL ' I I I I I Figure 4-A plot of dextrose concentration versus percent of procain-
0.986 0.988 0.990 0.992 0.994 arnide-dextrose complex formed after 2 days of storage (Solutions 5-9
MOLE FRACTION OF DEXTROSE Table I ) .
Figure 3-A plot of mole fraction of dextrose versus percent of the
complex formed after 4 days of storage (Solutions 22-25, Table I). 8 Brockway Glass Co., Brockway, Pa