A non-Aqueous Potentiometric Titration Method for Validation of Secnidazole from Pharmaceutical Dosages
Department of Chemistry, D. G. Ruparel College, Mahim, Mumbai 400016.
*Corresponding Author E-mail: drvinraj@gmail.com
ABSTRACT:
A sensitive non-aqueous potentiometric titration method was developed for quantitative determination of secnidazole from pharmaceutical dosage form. The titration was carried out using standardized 0.1 N perchloric acid. The proposed method was found to be precise with % RSD <1 (n = 6). The method showed strict linearity (r2> 0.999) between 20 % to 100 % of 500 mg of drug substance weight. The percentage recovery of secnidazole in the optimized method was between 99.643 to 100.505 %. The method is also found to be rugged when checked by different analysts and using different lots of reagents and different makes of titrators.
It is used mainly to treat intestinal ameobiasis, fiardiasis, trichomoniasis and bacterial vaginosis. All such disease symptoms are treated with a single once only dose of such drug.
According to the literature review several methods has been developed for drug, like spectroscopy methods1-3. HPLC4-9, HPTLC10 and miscellaneous11-15. A simple precise, rapid accurate and sensitive non-aqueous potentiometric titration method was developed for quantitative determination of secnidazole from bulk drug and pharmaceutical formulation. The developed method will useful for pharmaceutical industries and research organizations.
Structure of Secnidazole:
EXPERIMENTAL:
Instrumentation:
An potentiometric titrator was used (Lab- India auto titrator) for assay method development and validation.
A Shimadzu analytical balance with 0.01 mg was used.
Reagents and chemical:
Reference standard of secnidazole was obtained from reputed firm with certificate of analysis.
Potassium hydrogen phthalate, perchloric acid and glacial acetic acid of A. R. grade were used.
General procedure:
Standardization of 0.1 N perchloric acid:
About 0.350 mg of potassium hydrogen phthalate (previously powdered lightly, dried at 120oC for 2 hours) was weighed accurately into clean and dry titration jar. It was dissolved in 50 ml of glacial acetic acid. It was titrated with 0.1N perchloric acid in auto titrator. Blank determination was performed out for necessary correction. The titration was performed in duplicate.
One ml of 0.1 N HClO4 is equivalent to 0.2042 gm of potassium hydrogen phthalate (C8H5KO4)
W
Normality of perchloric acid = ----------------------------
B.R. x 0.2042
Where
W is weight of potassium hydrogen phthalate in g.
B.R. is burette reading in ml.
Quantitative determination of secnidazole:
About 0.500 g. of secnidazole test sample was weighted accurately into a clean and dried titration jar. It was dissolved in 35 ml. of anhydrous glacial acetic acid.
It was titrated with 0.1 N perchloric acid potentiometrically.
Blank determination was also carried out for necessary correction.
One ml of 1 N perchloric acid is equivalent to 0. 09959 g. of secnidazole
% (Percentage) Secnidazole on the dried basis was calculated as below
B.R. x N x 0.09959 x 100
% Assay = _____________________________
W
Where
B.R. is burette reading in ml at the potentiometric end point.
N is actual normality of 0.1 N perchloric acid.
W is weight of the sample taken in g.
RESULT AND DISCUSSION:
Determination of secnidazole:
The objective of this work was to determine accurately the content of secnidazole. The assay of secnidazole (on the dried basis) of various batches of secnidazole test sample was analyzed using the above method. It was in the range of 99.643 % to 100.505 %.
Analytical method validation:
The method precision was checked after analyzing six different preparations of homogeneous test sample of secnidazole. The % RSD of results obtained was found to be 0.6743. It confirms good precision of the method. The results are presented in table 1.
Linearity:
For the establishment of method linearity, five different weights of secnidazole test samples corresponding to 20 %,40 %, 60 %, 80 % and 100 % of the about weight (0.500 g.) were taken and analyzed for % (percentage) of secnidazole content. The results are in table 2.
TABLENO.1:METHODOFPRECISION
|
Weight of Secnidazole in g. |
Burette Reading in ml. |
Normality of perchloric acid |
% Assay |
|
0.100 |
10.1 |
0.09992 |
100.505 |
|
0.100 |
10.2 |
0.09992 |
101.500 |
|
0.100 |
10.1 |
0.09992 |
100.505 |
|
0.100 |
10.05 |
0.09992 |
100.007 |
|
0.100 |
9.9 |
0.09992 |
98.515 |
|
0.100 |
10.0 |
0.09992 |
99.510 |
|
Mean |
100.090 |
||
|
Standard deviation |
1.0156 |
||
|
% RSD |
1.0147 |
Table No. 2: Linearity
|
Level |
Weight of secnidazole in mg. |
Burette reading in ml. |
Normality of perchloric acid |
% Assay |
|
1 |
20 |
2.05 |
0.09992 |
100.5054313 |
|
2 |
40 |
4.03 |
0.09992 |
101.5005346 |
|
3 |
60 |
6.06 |
0.09992 |
100.5054313 |
|
4 |
80 |
8.09 |
0.09992 |
100.0078796 |
|
5 |
100 |
10.1 |
0.09992 |
98.51522472 |
|
Mean |
100.0908049 |
|||
|
Standard deviation |
1.015623032 |
|||
|
|
|
|
%RSD |
1.014701633 |
The potentiometric titration was conducted once at each level. Calibration curve was drawn by plotting test sample weight in gram on x axis and titre values on y axis.
The values of correlation coefficient, slope and intercept are given in table 3. and graph is given in fig no. 1.
Table No 3: Regression Values
|
Correlation Coefficient |
0.9999 |
|
Slope (m) |
0.100 |
|
Intercept (c) |
0.018 |
|
Regression equation |
y = 0.100x + 0.018 |
Accuracy and Recovery:
Accuracy was determined at five different levels i.e., 20 %, 40 %, 60 %, 80 % and 100 % of the nominal concentration. (0.500 g.) The titration was conducted in triplicate at each level and the titre value was recorded. The tire value obtained in linearity study was considered as true value during the calculation of percentage (%) recovery. The percentage recovery is calculated using following equation.
Titre value
Percentage recovery = --------------------------- x100
True titre value
The percentage range recovery of secnidazole was in 99.643 to 100.505 %. It confirms the accuracy of the proposed method. (Table 4).
Figno.1: Linearity graph
Table No 4 Accuracy and recovery
|
Level |
Burette reading in ml |
Weight of secnidazole added in g. |
Weight of Secnidazole found in g. |
% Assay |
Mean % assay |
|
1 |
2.02 |
0.02 |
2.04 |
100.505 |
|
|
2.03 |
0.02 |
2.02 |
101.002 |
100.505 |
|
|
2.01 |
0.02 |
2.01 |
100.007 |
|
|
|
2 |
4.01 |
0.04 |
3.99 |
99.759 |
|
|
4.05 |
0.04 |
4.08 |
100.754 |
100.339 |
|
|
4.04 |
0.04 |
4.06 |
100.505 |
|
|
|
3 |
6.03 |
0.06 |
6.03 |
100.007 |
|
|
6.01 |
0.06 |
6.02 |
99.676 |
100.007 |
|
|
6.05 |
0.06 |
6.06 |
100.339 |
|
|
|
4 |
8.05 |
0.08 |
8.05 |
100.132 |
|
|
8.06 |
0.08 |
8.07 |
100.256 |
100.007 |
|
|
8.01 |
0.08 |
7.98 |
99.634 |
||
|
5 |
10.02 |
0.1 |
9.99 |
99.709 |
|
|
10.01 |
0.1 |
9.97 |
99.609 |
99.643 |
|
|
10.01 |
0.1 |
9.95 |
99.609 |
Ruggedness:
The ruggedness of the method is defined as degree of reproducibility of results obtained by analysis of secnidazole sample under variety of normal test conditions such as different laboratories, different analysts and different lots of reagents. Quantitative determination of secnidazole was conducted potentiometrically on one laboratory. It was again tested in another laboratory using different instrument by different analyst. The assays obtained in two different laboratories were well in agreement. It proved ruggedness of the proposed method.
RESULT AND DISCUSSION:
The proposed method of non-aqueous potentiometric titration was found to be precise, accurate and rugged. The values of percentage recovery and standard deviation showed sensitivity. The method was completely validated. It showed satisfactory data for all the parameters of validation. Hence it can be applied for routine quality control application.
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Received on 10.12.2018 Modified on 13.01.2019
Accepted on 20.01.2019 ©AJRC All right reserved
Asian J. Research Chem. 2019; 12(1): 25-28.
DOI: 10.5958/0974-4150.2019.00006.3