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Terbinafină UV - Grupa 2
Terbinafină UV - Grupa 2
4, 1999
An ultraviolet spectrophotometric and a of TH in creams has not been reported. Spectroscopic (UV
nonaqueous volumetric method for determining and IR) and titrimetric techniques are used routinely in quality
terbinafine hydrochloride (TH) in pharmaceutical control because of their simplicity and rapidity. The objective
formulations are presented. The UV spectrophoto- of the present study was to develop a simple, sensitive, and ac-
metric procedure was developed for assay of TH in curate UV spectrophotometric method to quantitate TH in
raw materials, tablets, and creams. The method creams. Nonaqueous titration for determination of TH in raw
was tested for linearity (0.8–2.8 µg/mL, r = 0.9997), materials and tablets is also described.
recovery (102.00% for creams and 99.90% for tab-
Experimental
lets) and precision (101.3%, CV = 0.96%, n = 9, for
creams; 100.25%, CV = 1.08%, n = 9, for tablets). Chemicals and Reagents
The volumetric method involves titration of TH with
0.05M perchloric acid with crystal violet as indica- All reagents were analytical grade: 0.05M perchloric acid,
tor. This method was used for quantitative determi- 1% crystal violet, and 6% mercuric acetate in glacial acetic
nation of TH in raw materials and tablets. Mean re- acid. TH reference (assigned purity, 99.7%) was obtained
covery and precision were, respectively, 100.41 from Galena (São Paulo, Brazil). Pharmaceuticals containing
and 101.18% (CV = 1.64%, n = 9) for TH in tablets. terbinafine were obtained commercially. Tablets were
There were no significant differences between the claimed to contain 125 mg terbinafine (as base), and creams
proposed methods and a previously described were claimed to contain 1% TH.
high-performance liquid chromatographic method. Apparatus
The UV spectrophotometric and titrimetric meth-
ods are potentially useful for a routine laboratory A Shimadzu (Kyoto, Japan) UV-160 double-beam
because of their simplicity, rapidity, and accuracy. UV-visible spectrophotometer with a fixed slit width (2 nm)
and its recorder were used.
Spectrophotometry Standardization
erbinafine hydrochloride, (E)-N-(6,6-dimethyl-2-hepten-
Figure 1. Absorption spectrum of terbinafine hydrochloride in methanol (1.6 mg/mL): (A) reference, (B) tablets, and
(C) creams.
shaken for 30 min, the volume was made up to 50 mL with equivalent to 100 mg TH. This amount was transferred to a
methanol. This solution was filtered through filter paper 100 mL volumetric flask, and 60 mL methanol was added. Af-
(Schleicher & Schull, Germany). The first 10 mL of the fil- ter the flask was shaken, the volume was made up to 100.0 mL
trate was discarded. After filtration, dilutions were made with with methanol.
methanol to give a final concentration of 1.6 µg/mL. Nine de-
Recovery Tests
terminations were done in triplicate, and the absorbances of
the solutions were determined at 224 nm. Recovery of added reference TH was studied at 3 levels.
(b) Tablets.—Tablets were treated in the same manner as Portions of sample solutions (creams and tablets) containing
creams, except that the weight of pulverized tablets used was 1.2 µg TH/mL were transferred to a 50 mL volumetric flask.
UV spectrophotometry
Titrimetry
HPLC
1.0, 2.0, and 3.0 mL TH reference solution (20 µg/mL) were Method repeatability was studied by assaying 9 samples of
added to separate flasks to give final concentrations of 1.6, 2.0, creams or tablets, containing about the same concentration of
and 2.4 µg/mL, respectively. Recovery was calculated with the TH, during the same day, and under the same experimental
formula proposed by AOAC INTERNATIONAL (12). conditions. CVs were 0.96% for creams and 1.08% for tablets,
indicating good precision.
Titrimetry
Accuracy expresses the agreement between the accepted
To determine the average weight of a tablet, 20 tablets were value (either as conventional true value or an accepted refer-
weighed and powdered. In a 100 mL flask containing a mag- ence value) and the value found. Accuracy is reported as per-
netic bar, 100 mg of accurately weighed TH was dissolved in cent recovery of a known amount of analyte added to the sam-
30 mL acetic acid, and 10 mL 6% mercuric acetate solution ple (14). Mean recoveries were 102.00% for creams and
and 0.5 mL crystal violet solution (indicator) was added. The 99.90% for tablets. Results are comparable with declared
mixture was titrated with 0.05M perchloric acid until the color amounts and with those obtained by HPLC (Table 1). Analy-
changed to bluish green. The same procedure was used for sis of variance indicated no significant difference between UV
raw material. A blank determination was performed. spectrophotometry and HPLC (p < 0.01).
The other method described here is a nonaqueous
Recovery Test titrimetry. Most medicinal agents are weak acids or bases and
Accurately weighed amounts of powdered tablets equiva- can be assayed in a nonaqueous medium (15). Many salts of
lent to 100 mg TH were placed in 3 flasks. To each was added halogen acids may be titrated in acetic acid or acetic anhydride
12.5, 25, or 37.5 mg TH reference. Final concentrations were after addition of mercuric acetate, which removes the halide
equivalent to 90, 100, and 110%, respectively, of the declared ion as the unionized mercuric halide complex and introduces
amounts of TH in tablets. Recovery was calculated with the the acetate ion (16, 17). TH is an amine salt, and the reaction
formula proposed by AOAC INTERNATIONAL (12). in a nonaqueous medium between TH and 0.05M perchloric
acid provides a basis for precise and accurate determination of
Results and Discussion TH in raw materials and tablets.
Method validity was assessed by assay of tablets. The
Good planning is essential in the selection and develop- amount of TH found in tablets were 101.18% of the label claim,
ment of drug analysis methods. It is necessary to be able to with CV = 1.64%. Mean recovery was 100.41%. Levels deter-
quantitate with acceptable precision, accuracy, and reliabil- mined by the proposed method did not differ significantly (p <
ity within the budget and other considerations of the labora- 0.01) from those determined by HPLC (Table 1).
tory, such as complexity of the sample, intent of use, nature
of the drug, availability of apparatus, and specialist skills Conclusion
(13). Despite analytical methods based on chromatography,
spectrophotometric and nonaqueous volumetric methods The UV spectrophotometric and nonaqueous methods pre-
are still widely used because they are inexpensive and easy sented here are simple, precise, accurate, and convenient.
to perform. Therefore, they can be useful for routine analyses and qual-
One UV spectrophotometric method exists for TH deter- ity-control assays of TH in pharmaceutical formulations.
mination in tablets. The UV spectrophotometric method used
in the present study has an advantage over the reported References
method because it can be used to quantitate TH in creams and
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CARDOSO & SCHAPOVAL: JOURNAL OF AOAC INTERNATIONAL VOL. 82, NO. 4, 1999 833