New Mode Semi-Automated Turbidimetric Determination of Mefenamic Acid by Ayah 6SX1-ST-2D Solar cell -CFI Analyser

 

Raed F. Hassan

University of Baghdad, College of Science, Department of Chemistry

 

ABSTRACT:

The proposed method was carried out based on the interaction between the mefenamic acid and barium chloride in the basic medium to form a white precipitate of the binary ions complex. The turbidity values were determined by measuring the reflection of the incident light which is collided with the deposited particles at 0-180⁰ using Ayah 6SX1-T-2D solar cell CFIA. The plotted calibration graph has a linear range of (2-50 mmol/L) and the value of correlation coefficient is 0.9986 whereas the linearity percentage (r²%) is 99.71%, respectively. Detection limit (L.O.D) (S/N=3) = 240ng/sample of the gradual reduction of the lower concentration in linear dynamics ranging from the calibration graph. The proposed method was successfully applied for the quantitative determination of mefenamic acid (MFA) in three types of pharmaceutical samples. The proposed method was compared with the traditional method by using the standard addition (SA) method. The T test is used to show that there is no significant difference between the proposed method and the formal method with 95% confidence therefore, this method has suggested a new line for mefenamic acid determination.

 

 

INTRODUCTION:

The turbidity method can be defined scientifically that, is the measurement the scattering light due to the interaction between the sample molecule and the incident light, generally in liquid samples. The molecules which are optically active can easily absorb and scattering the light in a straight line. The physics definition of the turbidity is the decreasing in the transparency or cloudiness of water which is caused by the presence of dissolved suspended substance like calcium carbonate, magnesium carbonate, slite and clay.  These substances come from dyes, organic matter, organisms and plankton [1]. The mechanism of measuring the turbidity is made by calculating the total loss of light intensity which is scattered using the beam of the incident light and spectrophotometer at zero angles. Calculating the reflective index increment can provide important information about the quantitative determination of the molecular weight of the samples [2].

 

For example, if any sample molecule is dissolved in a liquid solution, and the incident light is applied, a part of that light will scatter in all directions of the solution. Measuring the attenuation of the light in the light direction can provide information about the amount of turbidity that is existed by the dissolved sample [3]. Mefenamic acid [2,3 - dimethyl phenylamine] benzoic acid (MFA) [4]. The following structure is shown in Figure (1). It is used to treat osteoarthritis, rheumatoid arthritis and other musculoskeletal diseases [5]. It is an anthracitic acid derivative and is a member of the fenamate group of non-steroidal anti-inflammatory drugs (NSAIDs) [6]. Several analytical methods have been developed to estimate mefenamic acid in pure form and in doses including: - HPLC [7-13], spectrophotometer [14-20], atomic absorption spectrometer [21-23] and flow injection analysis [24-26]. The injection method of reverse injection has an excellent Have a great sensitivity in determine the mefenamic acid in different types of samples like pharmaceutical and pure samples. This work is simple, fast, evolving and sensitive depends on the composition of particles deposited in the interaction between MFA and barium chloride in an average alkaline product to white precipitate. The resulting light attenuation will be measured by Ayah 6SX1-ST-2D Solar cell -CFI Analyser.   

 

Figure 1: Chemical structure of mefenamic acid (MFA)

 

EXPERIMENTAL:

The Chemicals:

All the prepared solutions which were used were from of analytical reagent and double distilled water during this paper. Mefenamic acid (C₁₅H₁₅NO₂.HCl, 241.285 g/mol), (0.1mol/L) 2.4129g/100mL in (NaOH, 40g/mol, BDH, 0.1mol/L) and 0.4g in 100mL distilled water (Standardized with HCl (0.1mol/L solution) were prepared. A stock solution of barium chloride (BDH), 244.27g/mol) (0.2mol/L) was prepared by weighting 4.8854g in 100mL distilled water.  

 

Preparation of sample:

Twenties tablets were weighted and grinded from each of the drug supplier (Ponslab- Indi), (Ponstidin, SDI, Iraq) and (Ponstan frte-pfizer - Switzerland) containing 500 mg of mefenamic acid were weight i.e:  0.8549, 0.7902 and   0.8815g which is equivalent to 0.6032g to ingredient (50mmol/L). Then the powder was dissolved in sodium hydroxide and filtered in order to remove all the undissolved residue that might affect the response. The volume was completed with sodium hydroxide to obtaining the target concentration.  

 

Apparatus and Manifold:

The flow system consist of numbers of parts that were connected together to accomplish a complete flow system to determine MFA. These parts are. Peristaltic pump: (ISMATEC type ISM 796 made in Switzerland) 4 channels, various speeds were applied during this experiment. Different connection tubes were used in the manifold system which made from rubber, silicon, Teflon and poly propylene which has 0.5-1 mm dimeter. Rotary Six Port Injection Valve (Teflon): six ports medium pressure (model I D E X corporation, USA) valve was used with a variables sample volumes, fixed on the carrier stream line. Y- Junction Point: homemade liquid junction point (made by Dr. Issam M. A. Shakir) made of methylmethacrylate for the mixing of chemical reactants in reaction pattern. X, Y-t Two Pens Synchronized Potentiometric Recorder: the output of the system contains of X, Y-t potientiometric recorder (Type KOMPENSO GRAPH C-1032, Germany. Measuring System: homemade instrument (Ayah 6SX1-ST-2D Solar cell) capable in measuring Output of peak height. The flow system used shown schematically in Figure (2).

 

Figure 2: Shows the diagram of flow injection analysis system

 

Methodology:

The whole reaction manifold system is determined to determine the mefenamic acid via sedimentation with barium chloride in the alkaline medium is consisted of double lines as seen in Figure (2). The first line illustrates the carrier stream of NaOH (5mmol/L) at flow rate 2.3ml/min using the injection valve to carry out the mefenamic acid. While the second line supplies the barium chloride solution (0.5mmol/L). at 2.4mL/min. The sample volume is 100μl. Both the two lines meet and mixes together at the Y-junction. The peak height output is followed by a homemade instrument (Ayah 6SX1-ST-2D Solar cell CFI Analyser). A different responses were seen by emitter diode (Six snow- white light) during the reactions. All the solutions that applied in the experiment are triplet tested before using it. The potentiometric recorder type (X-t) was used to record all the peaks high in mV by measure the reflection light at 0-180. The suggested proposed mechanism for the composite configuration is shown in Scheme no.1.

  

Scheme no. 1-Proposed mechanism for the reaction between MFA and BaCl₂   

 

Variable Optimization:

Many of chemical parameters such as regents and concentrations were used in order to conduct the precipitation reactions in addition to the physical parameters such as sample volumes and flow rate were investigated using second line manifold system as shown if Figure (2).

 

Table 1: The effect of BaCl₂ on the peaks measurement

 

Table 2: The effect of Salts on the measurement of peak height

 

Optimization of Chemical Parameter:

Effect of Barium Chloride Concentration:

A series of solutions (0.01-1mmol/L) were prepared by 75µL volume of MFA as an injected sample volume. A flow rate of 2.1ml/min was used as a carrier stream (distilled water) and 2.2ml/min as a flow rate for the reagent. Each of measurements was repeated four times. Table 1 summarizes the results obtained. It can be observed that 0. 5mmol/L of barium chloride give high peak so it was considered the optimum concentration for further work. Figure 3A, B are shown responses profiles and optimum concentration of BaCl₂.

 

 

Figure (3A): Effect of variation of BaCl₂ Concentration on response profile

 

Figure (3B): Effect of variation of BaCl₂ concentration on precipitation of mefenamic acid

 

Effect of Salts on Precipitation Reaction

A series of salts (H₂O, KNO₃, KCl, KBr, NH₄Cl, CH₃COONa and CH₃COONH₄) (50 mmol/L) were prepared. Using 75µL MFA as injected sample volume. 2.1 ml/min was used as a carrier stream (distilled water) and 2.2 ml/min (0.5mmol/L BaCl₂) as the second line flow. Each of obtained measurement was repeated for three successive times. Table no.2 summarizes the results obtained. A study was noticed that the use of distilled water gives a better response profile. Figure (4A, B) shows the detailed profile. The use of salts gave unsatisfactory result. Therefore no salt was used. While maintain use of distilled water for further work.

 

Table 3: The effect of NaOH on the measurement of peak height

 

 

Figure 4A: Effect of variation of Salts on response profile

 

Figure 4B: Effect of variation of Salts on Output of peak height

 

Effect of basic media on Precipitation Reaction:

The effect basic of the reaction medium for the determination of MFA was prepared different concentrations of NaOH at the range (5- 500)mmol/L as a carrier stream line flow rate 2.1ml/min and 2.2ml/min  for reagent line represented the optimum concentration of barium chloride (0.5mmol/L) with 75μL sample volume to injected MFA. The obtained results are shown in Table 3 and the responses profiles are shown in Figure 5. It can be seen that the distilled water is given Output of peak height (1108mV), while the (NaOH) given (1240 mV) so that was chosen as the best medium and due to the most suitable for completing reaction of barium chloride with MFA.  Therefore 5mmol/L of NaOH was regarded as the optimum basic concentration medium for the work conducted in this research.  

 

 

Figure 5: Effect of variation of NaOH concentration on response profile

 

Optimization of Physical Parameter:

- The Flow Rate Effect:

A set of experiments were conducted in order to optimize of the preferred flow rate after using different flow rates (0.5-2.9mL/min) for the carrier stream 5mmol/L NaOH (first line) and (0.5-3.1mL/min) for reagent 0.5mmol/L BaCl₂ (second line) controlled by the peristaltic pump, Using MFA (50 mmol/L) at 75μL sample volume The results obtained were summarized in Table 4. It was observed that at slow flow rate, there is increasing in the dilution and dispersion which might cause an increase in base width ∆tB of output of peak height. Figure (6) shows the optimum flow rate (2.3 and 2.4)mL/min for the carrier stream and BaCl₂ respectively used was based on obtaining of sharp maxima and regular response but it is not very high because the precipitate particles departure speed from the cell at a short time. On this basis a compromise were chosen as optimum flow rate during this experiment.

Table 4: The effect of different flow rates precipitation system of mefenamic acid

Peristaltic pump (indication approximate)	Flow Rate (mL.min-1)		Output of peak height `yi (n=3) (mV)	% R.S.D	Confidence interval of the mean	Base width ΔtB (sec)	t* (sec)
	5 mmol/L NaOH Carrier stream	0.5 mmol/L BaCl2 precipitation agent
5	0.5	0.5	1336	0.24	1336±7.98	192	60
10	0.9	0.9	1160	0.18	1160±5.24	162	48
15	1.2	1.3	1168	0.16	1168±4.77	126	42
17	1.5	1.4	1080	0.11	1080±3.01	114	36
20	1.7	1.7	1096	0.12	1096±3.28	96	30
23	1.9	1.9	1136	0.10	1136±2.73	78	24
25	2.1	2.2	1236	0.09	1236±2.71	60	21
27	2.2	2.3	1248	0.09	1248±2.68	48	18
30	2.3	2.4	1264	0.09	1264±2.76	36	12
35	2.5	2.5	1168	0.10	1168±3.01	30	9
40	2.9	3.1	1544	0.08	1544±3.21	24	6

t* = Departure time for sample segment from injection valve to the measuring cell

 

Figure 6: Effect of variation of flow rate versus Output of peak height

 

 

 

Effect of the Sample Volume

Under the optimum conditions which were selected during the experiments. The injection volumes were varied from 25 to 250µL by applying the open valve mode i.e. allowance for continuous purge system of sample. That any increase in volume of sample up to 100 μL lead to an increase in the Output of peak height but gave a distorted profile with a time consuming measurements which was can be probably attributed to long time duration of sample segment in front of detector. The results obtained were summarized in Figure 7A. While 100μL volume of sample gave regular responses as shown in Figure 7B.

 

 

Figure 7B: Response profile of variation in sample volume(μL)

 

 

Figure 7A: The effect of the variation sample volume on peak height

 

Calibration curve for variation of MFA concentration versus Output of peak height:

A series of MFA solutions which is ranged from 2-50 mmol/L were prepared, by the optimum physical and chemical parameters. The results for variation of MFA concentrations were prepared in order to use them in the preparation of scatter plot diagram followed by of plotting the calibration graph. Tabulated the obtained results in Table (5-A) and clarified in Figure (8) which shows the variation responses with different concentrations of MFA. Analysis of variance was inserted in Table (5-B) which indicated. From the results it can conclude that there is a significant relation between the output of peak height and the concentrations of MFA.

 

 

Figure 8: Calibration graph for Mefenamic acid concentration in mmol/L

 

Table 5-A: Summary of calibration graph results for the estimation of Mefenamic acid by FIA method

Measured [MFA] mmol/L	[MFA] range for n=12 mmol/L	y^(mV)=a±Sat+b±Sbt [MFA)] mmol/L at confidence interval 95%, n-2	r, r2, r2%	ttab.	tcal
				at 95%, n-2
2-50	2-50	75.75±39.10+31.19±1.18 [MFA] mmol/L	0.9986 0.9971 99.71%	2.228 << 58.66

t _tab= t_0.05/2,10= 2.228

 

Table 5-B: ANOVA for linear equation results [27-29]

Source	Sum of squares	Df	Mean square	Fstat.=
Regr.	3217363.40	n1=1	3217363.40	3480.78>> 4.965
Error	9243.239	n2=10	924.3239
Total	3226606.639	11

F¹₁₀ =4.965

 

 

Table 6: Limit of detection of Mefemanig acid at optimum parameters for MFA- BaCl₂-OH system

Gradual dilution for the lowest concentration of calibration graph	slope	Linear equation y^(mV) = yB+3SB
0.01mmol/L 240ng/sample	0.0289mmol/L 697.31ng/sample	2.9240mmol/L 70.55 µg/sample

x= value of L.O.D. based on slope.      S_B = standard deviation of blank solution

y_B= average response for the blank solution (equivalent to intercept in straight line equation)

 

Table 7: Repeatability of Mefemanic acid results

[MFA] mmol/L	Number of measuring (n)	Output of peak height `yi (n=8) (mV)	Repeatability R.S.D.%	Confidence interval of the mean
500	6	1636	0.14	1636± 2.35

 

 

 

Limit of detection Study

The limit of detection of the Mefenamic acid (MFA) was calculated throughout using three different approach as shown in Table 6 (100 µl injected sample volume).

determination of MFA via measurements of the precipitate formed by Ba⁺²(0.5 mmol/L) - MFA (50 mmol/L) - OH^-1(5 mmol/L) system. Table no. 7 show the results obtained while Figure (9) show the response profile.

 

Figure 9: Response profile of repeatable measurements of MFA (50 mmol/L) using homemade Ayah-6SX1-ST-2D Solar

cell -CFI analyser

Analytical Application:

The developed method was applied to drugs available in the market as tablets form; (Ponstidin- SDI, Iraq), (Ponslab- Indi) and (Ponstan frte-pfizer - Switzerland). The methods were used firstly method was Turbidimetric - Continuous flow injection analysis, While the second method was classical UV-Vis spectrophotometric method [30]. It was compared the results which were obtained from the standard addition method by Ayah 6SX1-ST-2D solar cell-CFI with standard method. Table 8 provide the information about drug dose, the names and results at confidence interval 95%, using paired t-test between the proposed method and classical method; as shown in Table 9 which indicate that there is almost no significant different between proposed method FIA and standard method at 95% confidence interval as the obtained t-test values which was less than tabulated t-test value.

 

Table 8: The determined quantities of MFA in pharmaceutical samples

sample no	commerical name, content company, country	Ayah 6SX1-ST-2D solar CFIA (mV)
		[Mefenamic acid] mmol/L					Equation of standarad addition curve at 95% for n-2 Ŷi(mV)=a±sat+b±sbt[MFA] mmol/L	r r2 r2%	Practical conc. mmol/L
		0	10	12	14	16
									in 25 ml
									in 100 ml
1	Ponstidin, 500 mg, SDI, Iraq	95	520	608	709	780	93.62± 23.55 + 43.15± 2.00[MFA] mmol/L	0.9997 0.9994 99.94%	2.1696 mmol/L
									10.8480 mmol/L
2	Ponstan*Fort 500 mg, Pfizer; Switzerland	160	876	1040	1180	1360	151.67 ± 53.40 + 74.19 ± 4.53[MFA] mmol/L	0.9995 0.9990 99.90%	2.0444 mmol/L
									10.2220 mmol/L
3	Ponslab, 500 mg, KLAB, India	60	360	416	482	512	64.45 ± 37.61+ 29.00 ± 3.19[MFA] mmol/L	0.9982 0.9964 99.64%	2.2224 mmol/L
									11.1120 mmol/L

Ŷi*= estimated value for absorbance, r= Correlation coefficient, r²= coefficient of determination (C.O.D), r²%= Linearity percentage

 

Table 9: The paired t-test, efficiency and experimental content of MFA in three samples

Sample no	Confidence interval for the average weight of tablets   i±1.96 σn-1 / at 95%(g)	Theoretical content for the active ingredient i±1.96 ?n-1/ at 95% ( mg)	Sample weight equivalent to 0.60320g (50 mmol/L) of the active ingredient wi (g)	Practical weight content of active ingredient Ayah 6SX1-ST-2D solar CFIA (mV)		Efficiency of determination (Rec%)	Paired t-test
				In 100 ml of sample  i± t0.05/2,n-1 σn-1/ at 95% (g)	in tablets  i± t0.05/2,n-1 σn-1/ at 95% (mg)		Individual comparison ( i - μₒ)√n/σn-1 Ayah 6SX1-ST-2 D Solar cell-CFI Analyser with Quoted value t0.05/2,2= 4.303	Comparison between two method
						Ayah 6SX1-ST-2D solar CFIA (mV)
						UV-Vis SP. (classical method for absorbance measurement)[30]		Xd	(σn-1)	tcal =  /σn-1 at 95 %
1	0.65495 ± 0.00346	500 ± 2.6414	0.7902	0.6575 ± 0.139	545 ± 115.217	109 %	1.681  4.303	71.524	62.167	2.792  4.303
						94.70%
2	0.73065 ± 0.00177	500 ± 1.2113	0.8815	0.6153 ± 0.080	510 ± 66.309	102 %	0.649   4.303	19.779
						98.04%
3	0.70862 ± 0.00331	500 ± 2.3355	0.8549	0.6696 ± 0.169	555 ± 140.076	111 %	1.690  4.303	95.197
						91.96%

Xd: Difference between two method, (X ̅ d): difference mean, σn-1: Difference standard deviation, n=3 for individual & n=3 for comparison between two method, t_0.025,2=4. 303

 

CONCLUSION:

The procedure and the conducted studies resulted in the characterization of a highly sensitive (240 ng/sample) methodology through the precipitation of the drug mefenamic acid via a precipitating agent of barium chloride in a very delicate advanced technique of instrumentation using six white snow light emitting diode with two solar cell. An extended calibration graph was obtained compared with available classical methods.

 

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Received on 31.03.2019           Modified on 20.05.2019

Accepted on 30.07.2019         © RJPT All right reserved