FT-IR Spectroscopic method for Analysis of dimethylsulfone

Nahla N Salama et al. / Journal of Pharmacy Research 2011,4(4),964-966
Research Article
ISSN: 0974-6943
Available online through
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FT-IR Spectroscopic method for Analysis of dimethylsulfone
Nahla N Salama a,*, Mohammed El Reis a, Safaa Toubar b, Maha AbdEl Hamide a , Mohammed Walashc
a
Pharmaceutical Chemistry Department, National Organization For Drug Control and Research, Egypt
b
Analytical Chemistry Department, Faculty of Pharmacy, Helwan University
c
Analytical Chemistry Department, Faculty of Pharmacy, Mansoura University
Received on: 20-01-2011; Revised on: 18-02-2011; Accepted on:16-03-2011
ABSTRACT
A rapid FTIR spectroscopic method was developed and validated for quantitative analysis of dimethylsulfone(MSM), in drug substance and product. The method involves the extraction of
the active ingredient with chloroform and the measurement of the area of the infrared band corresponding to the sulfonyl group centered at 1141 cm-1. The specificity, linearity, detection limits,
precision and accuracy of the calibration curve, and data manipulation were determined in order to validate the method. Moreover, the statistical results were compared with the quantification
of MSM through GC detection. The linearity range was found to be 25 - 200 µg/220 mg KBr. The recovery values obtained in the analysis of drug product are within 98.90 - 100.50 % range.
The technique is reliable and useful for quality control for monitoring the adulterations of pure drug.
Key words: FTIR, Dimethylsulfone, Drug product, Validation
1. Introduction
Infrared spectrometry (IR) provides a useful way for the identification of drugs.[1-4] However, the
traditional techniques employed to obtain the IR spectra, such as alkali halides disks, mulls
and thin films, are sometimes not adequate for quantitative analysis. Fourier Transform (FTIR) permits continuous monitoring of the spectral baseline and simultaneous analysis of
different components of the same sample.[5-8] Dimethylsulfone(MSM), is an anti-inflammatory
drug used in the treatment of osteoarthritis and arthritis.[9-12] It is non official drug. The
literature comprises two GC methods for its analysis.[13,14]
CH3-SO2-CH3
Dimethylsulfone
A calibration curve was constructed relating to absorbance versus drug concentration in µg
MSM / 220 mg KBr.
2.6. Application to drug product
Six tablets of MSM were accurately weighed and finely powdered. Aliquots equivalent to
about 10 mg of MSM were accurately weighed and transferred to 50 mL beaker, and 40 mL
chloroform were added. The beaker was covered with glass watch and the solution was stirred
with magnetic stirrer for 60 mins. Then the solution was quantitatively transferred to 50 mL
volumetric flask and the volume was completed to the mark with chloroform.The solution was
filtered and the procedure was followed as mentioned under 2.5.
The present work outlines the development of quantitative analysis method for MSM in drug
substance and product. To develop the quantitative analysis method, a number of standard
powder ‘solutions’ of known concentration are prepared and spectra are collected from aliquots
of the standards. Specified absorption bands are identified and the peak heights or areas
calculated for the various standards. The method has several advantages over the reported GC
method, where there is no need for method development, and the time of analysis is 5 - 10 min.
2.7. Method validation
2.7.1. Linearity
Five µL of working standard solutions of MSM in concentration range 25-200 µg was applied
to 220 mg KBr, and the specified conditions was adopted as mentioned under 2.5. The
calibration curve representing the relationship between absorbance and the corresponding
concentrations of the drug was plotted and the regression equation was computed.
2. Experimental
2.7.2. Limit of detection and quantification
According to ICH recommendation [15,16] the approach based on the standard deviation of the
response and the slope of the calibration curve, was used for determining the detection limits
by applying the following equation:
2.1. Instruments
The IR analysis were performed using the Thermo-Fischer Scientific Nicolt 6700 FTIR
Omnic 8 (USA), quantitative analysis of solution of MSM in chloroform were performed.
2.2. Materials and reagents
Dimethylsulfone ( B. No: 006705), was obtained from Eva-Pharm Co., Egypt, its purity was
found to be 99.00% according to the manufacturer GC-method. MSM tablet( B. No: 702180)
labeled to contain 1000 mg MSM/tablet was purchased from the market. Chloroform (Fischer
Scientific, UK) and KBr ( Sigma-Aldrich, Germany) were used in the study. All chemicals
were of analytical grade if not stated otherwise.
2.3. MSM stock standard solution (0.2 mg mL-1)
An accurately weighed amount about 10 mg of MSM was transferred to 50 mL volumetric
flask, dissolved in chloroform. Then the volume was completed with chloroform.
2.4. MSM working standard solutions
Working standard solutions were accurately prepared in concentration ranges of 25-200 µg /220
mg KBr from MSM stock standard solution (0.2 mg mL-1).
2.5. FT-IR procedure
Aliquots equivalent to 25-200 µg working standard solution of MSM were accurately transferred to IR mortar containing 220 mg KBr. The solvent was air-dried while triturating and
mixing. A homogeneous disc was prepared from the completely dried and finely ground
powder. The IR spectrum was recorded for each disc, at resolution of 4 cm-1.The absorbance of
the band due to sulfonyl group of MSM at 1141 cm-1 was calculated by applying the base line
technique.
*Corresponding author.
Nahla N Salama
Pharmaceutical Chemistry Department,
National Organization For Drug Control and Research, Egypt
LOD = 3 s / S, Where s = standard deviation of regression lines and S = slope of regression
line.
The LOQ = 10 s / S, LOQ of an individual analytical procedure is the lowest amount of analyte
in a sample which can be quantitatively determined with suitable precision and accuracy.
2.7.3. Accuracy
The previously mentioned procedure under linearity was repeated four times for five different
concentrations within the linearity range. The concentrations were calculated from the regression equation. The recovery percentages and the mean recovery were then calculated.
2.7.4. Precision
For evaluation of precision, repeatability & intermediately precision were performed. Repeatability was evaluated by assaying freshly prepared solutions in triplicate at concentrations 50,
75, 100 µg/220 mg KBr of the drug substance, using pervious mentioned procedure under
linearity ( intra- assay precision ). The intermediate precision of the proposed method was
evaluated by assaying freshly prepared solutions in triplicate at concentrations 50, 75, 100 µg/
220 mg KBr of the drug substance for three days. The relative standard deviation was
calculated.
2.7.5. Standard Addition Technique
The specified FTIR-Spectroscopic conditions were adopted to the analysis of the studied drug
in its drug product, the standard addition technique was applied. The concentrations were
calculated from the regression equation. The percentage recoveries were then calculated.
3. RESULTS AND DISCUSSION
Although IR –Spectroscopic is mainly described to identify drugs and chemicals, yet the
introduction of FTIR technique with its particular mathematical treatment of data, results in
improved sensitivity and reproducibility.
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3.1. Spectral characterization
The FTIR spectrum of MSM substance , product, excipient and expire batch were presented
in Fig (1, 2, 3, 4 respectively), which show characteristic bands checking the purity and
identity of the drug, among which there was a sharp and intense one at 1141 cm-1 due to its
sulfonyl group stretching.
3.2. Method validation
The results of assay validation were assessed and represented in Table (1) The linearity of
calibration curve was validated by high correlation coefficients ( 0.9968), with linear regression
equation was computed and found to be:
Y= 0.0045 X – 0.0258
Where Y = IR- absorbance at 1141 cm-1 , and X =concentration in µg/220 mg KBr Figure (4).
The limits of detection and quantification were found to be from 12.30 - 41.01 µg/220 mg KBr
respectively as stated in Table 1.
Table 1. Validation report for FT-IR spectroscopic method for determination of MSM in drug
substance
Figure 1. The FT-IR spectra of MSM substance at 1141 cm -1.
Parameters
Results
Linearity range(µg/220 mg KBr)
LOD µg/220 mg KBr
LOQ µg/220 mg KBr
Regression
Slope
SE of slope
Intercept
SE of intercept
Correlation coefficient
SE of estimation
25 – 200
12.30
41.01
0.004529
0.000151
-0.02518
0.018574
0.9983
0.021624
The accuracy was evaluated by determination of different concentrations of drug substance. The
mean percentage recoveries and relative standard deviations were evaluated and the results are
stated in Table 2.
Table 2. Recovery of the proposed FT-IR Spectroscopic method for determination of MSM
in drug substance
Figure 2. The FT-IR spectra of MSM product at 1141 cm -1.
Amount taken
µg/220 mg KBr
Found µg/220 mg
KBr
Recovery*
%
25
50
75
100
150
Mean
RSD%
24.53
49.52
73.76
100.28
147.03
98.13
99.04
98.34
100.28
98.02
98.76
0.95
*Mean of six determinations
The precision of the method (within-assay and between-assay) was determined for MSM
concentrations cited in Table 3. The within-assay precision was assessed by analyzing three
concentration levels in triplicate in a single assay run. The between-assays precision was
assessed by analyzing the same sample, in triplicate, in three separate assay runs. The method,
gave satisfactory results. The relative standard deviations (RSD) were less than 2% (Table 3).
This level of precision of the proposed method was adequate for the quality control analysis of
MSM.
Table (3): Intra and inter-day precision and accuracy of the proposed FT-IR spectroscopic
method for determination of MSM in drug substance
Figure 3. The FT-IR spectra of excipient at 1072 cm -1.
Drug
substance
Conc.
µg/220mg KBr
Precisiona RSD%
Intra
Inter
Accuracya RE%
Intra
Inter
MSM
50
75
1.50
1.84
0.83
1.73
-0.59
-0.06
0.46
-0.06
100
1.39
1.25
1.30
-0.19
a
n=6
The specificity and selectivity of the proposed method were demonstrated when analyzing the
expire batch, where complete difference between expire and non expire batches are noticed(Figure
4,2).
The results obtained by applying the proposed FTIR method for the analysis of the studied
compound in drug substance was statistically compared with the method supplied by
manufacture .[17] The values of the calculated F and t are less than the tabulated ones which
reveals that there is no significant difference with respect to accuracy and precision[18] as shown
in Table 4 . The method was further assessed by application of the standard addition technique
as shown in Table 5 .
Table( 4): Statistical comparison between the proposed FT-IR spectroscopic method and
manufacturer method for determination of MSM in drug substance
Figure 4. The FT-IR spectra of expire batch .
Values
FT-IR spectroscopic
method
Manufacturer
method*
Mean
Standard deviation (SD)
Variance(S 2 )
n
F (5.05)**
t(1.8122)**
99.57
0.6
0.36
6
2.46
0.744
99.36
0.38
0.146
6
* Manufacturer GC method supplied by personal communication.** Values between parentheses represents the tabulated t and F values at P=95%.
Journal of Pharmacy Research Vol.4.Issue 4. April 2011
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Nahla N Salama et al. / Journal of Pharmacy Research 2011,4(4),964-966
Table 5. Results of application of standard addition technique by the proposed FT-IR spectroscopic method
Preparation
Amount taken
(µg/220mg KBr)
Pure added
(µg/220mg KBr)
Found
recovery*% ± RSD
MSM®
(1000 mg
MSM/tab)
50
25
50
75
100
150
100.50 ± 2.00
100.59 ± 1.50
100.06 ± 1.84
98.70 ± 1.39
100.21 ± 2.00
*Mean of six determinations.
The method was applied on drug product and compared with the methods supplied by
manufacturer, as shown in Table 6.
Table 6. Application of the proposed FT-IR spectroscopic method for determination of
MSM in drug product
MSM®
Proposed FTIR Spectroscopic method
(1000 mg of MSM/tab) Recovery of claimed amount*% ± RSD
92.49 ± 2.00
Manufacturer **
Recovery of claimed amount*% ±RSD
94.56 ± 0.85
* Average of six determinations.** Manufacturer GC method supplied by personal communication.
CONCLUSION
Infrared quantitative analysis is an everyday requirement for the analytical laboratory. It is clear
that FT-IR spectrometry is capable of direct determination of MSM in drug substance and
product. The recommended method is simple, precise and not time-consuming compared to
the chromatographic GC methods that exist in literature. Quantification could be done in
about 5 - 15 minutes, including sample preparation and spectral acquisition. The technique is
reliable for quality control of drug and monitoring the adulterations of sample.
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Source of support: Nil, Conflict of interest: None Declared
Journal of Pharmacy Research Vol.4.Issue 4. April 2011
964-966