Abstract
This research aims at using a novel algorithm to determine the concentration of mefenamic acid (MA) in solutions using merging zone-continuous flow injection. The MA concentration in aqueous solutions was determined using this technology, and the results obtained using this method were compared to those obtained using more conventional methods. All flow injection analyses were carried out utilizing a Rheodyne valve 7725, a Rabbit peristaltic pump, a BioLogic QuadTec UV-Vis Detector, and a Sartorius CPA2P Competence Analytical Balance, as well as a Sartorius CPA2P Competence Analytical Balance. The data is then received by a signal detector and a specialized software spectrometer. A spectroscopic scan is used to determine the maximum wavelength of the product, a calibration curve is created, and measurements are taken to estimate the drug's absolute concentrations in aqueous solutions. The detection and quantitative limits were set to 0.021 and 0.071 parts per million. This treatment is popular and could be a good alternative to conventional methods because it is simple, rapid, precise, inexpensive, and adaptable.
HIGHLIGHTS
A novel merging zone-continuous flow injection was used to measure the mefenamic acid in solutions.
The obtained detection and quantitative limits were set to 0.021 and 0.071 parts per million.
This method could be a good alternative to the conventional methods because it is simple, rapid, precise, inexpensive, and adaptable.
INTRODUCTION
In past decades, aquatic pollution by residual pharmaceuticals and personal care products (PPCPs) have been a major concern. Discharges from wastewater treatment plants (WWTPs) have been recognized as one of the most important sources of PPCPs. Previous reports have detected PPCPs in aquatic environments such as wastewater effluent, rivers, and fish samples. Although concentrations of many PPCPs in natural aquatic environments are generally in the range from parts per trillion (ng L1) to parts per billion (μg L1), several compounds have been shown to remain in environments at levels that can pose potential ecological risks (Sankoda et al. 2019). Among PPCPs, mefenamic acid (MA) is a nonsteroidal anti-inflammatory drug (NSAID) that belongs to the medications’ anthranilic acid derivatives (or fenamate) class and has been frequently detected in aquatic environments due to the low removal efficiency of WWTP processes. It treats mild to moderate pain and is a member of the anthranilic acid derivatives (or fenamate) family (Morcoss et al. 2017). It is not extensively used in the United States because of its adverse side effects and expensive cost compared to other NSAIDs (García et al. 2001; Savjani et al. 2017). Specifically, it is known by the scientific name dimethylphenylaminobenzoic acid, which is the name derived. It was first made available to the public by Parke-Davis in the 1960s, and it has since been widely distributed. Meftal is a brand name for a medication genericized in the 1980s and available under various brand names. Those who have previously experienced allergic reactions such as urticaria and asthma in response to this or other NSAIDs (for example, aspirin), those who have peptic ulcers or chronic inflammation of the digestive tract, those who have kidney or liver disease, and those who are pregnant or breastfeeding should not take this medication (Cimolai 2013). MA has been linked to minor side effects (Ozgoli et al. 2009), including headaches, anxiety, nausea, and vomiting. Although toxic epidermal necrolysis and blood cell abnormalities such as agranulocytosis are rare side effects, they can be life-threatening. Because of this, acute liver injury has been linked to the condition over time (Sabry 1998). The term ‘premature closure of the ductus arteriosus during pregnancy’ was added to the label in the United States in 2008 (Gewillig et al. 2009). Because of low amniotic fluid levels in pregnant women (Ovayolu et al. 2020), by October 2020, the FDA has mandated that all NSAIDs be amended to contain a warning about the risk of renal problems in unborn neonates (Gewillig et al. 2009). Women who are 20 weeks or more pregnant, according to experts, should avoid taking NSAIDs (Gewillig et al. 2009). This medication's interactions with other NSAIDs are comparable to those of those other medications (NSAIDs). MA has been shown to interfere with the anti-clotting activity of aspirin. Its ability to separate warfarin and phenprocoumon from plasma proteins enhances its anticoagulant properties. Some studies have linked inflammatory drugs such as corticosteroids and selective serotonin reuptake inhibitors to an increased risk of gastrointestinal ulcers. If the amount of methotrexate and lithium excreted by the kidneys is reduced, this may have negative repercussions. The toxicity of cyclosporin and tacrolimus may be exacerbated by using this medicine. Inhibitors, sartans, and diuretics are antihypertensive drugs that have reduced efficacy when combined with these other medications, and the risk of kidney damage is increased (de Abajo et al. 1999; de Abajo 2011).
The treatment approaches of MA from wastewater are not limited to electro-Fenton degradation (Dolatabadi et al. 2020), activated charcoal, and a micelle-clay complex (Khalaf et al. 2013), chlorine dioxide (Hey et al. 2012), biological treatment (Hata et al. 2010; Rosal et al. 2010; Deepa et al. 2021), membranes (Kimura et al. 2005; Radjenović et al. 2009) and oxidation (Colombo et al. 2016; Deepa et al. 2021). Additionally, the electrochemical method is attracting the attention of researchers because of its cheapness (Hashim et al. 2021b; Arab et al. 2022) and environmental safety (Abdulhadi et al. 2021; Hashim et al. 2021a); therefore, it can be a suggestion in this paper for removing MA from wastewater.
Many approaches for assessing MA in pharmaceutical formulations and biological materials have been developed and published. A few examples of these approaches are chemiluminescence, catalytic degradation (Amini & Mengelizadeh 2020), electrochemical sensors (Hasanzadeh et al. 2012; Bukkitgar et al. 2014; Valian et al. 2022), spectrophotometry, spectrofluorometry, high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) (Ahrer et al. 2001; Jaiswal et al. 2007; Madrakian et al. 2009). As a result, the current research is focused on detecting the concentration of MA in aqueous solutions utilizing a flow injection approach and new software created by (Al Sultani et al. 2019), branded G-chrom V1.5, which was just released.
MATERIALS AND METHODS
Reagents and substances
Unless otherwise stated, all analytical-grade chemicals were used, and double-distilled water was used for all processes from reagent dilution to sample processing. The reference 1,2-naphthoquinone-4-sulfonate (NQS) provided by Aldrich, and the drug was obtained from Samara, an Iraqi state-owned pharmaceutical enterprise (SDI).
Preparation of MA, NQS, and experimental work
It was possible to make MA at a concentration of 50 parts per million (ppm) by dissolving 5 mg (0.005 gm) of MA in 25 mL distilled water and diluting the solution with distilled water 100 mL in a volumetric flask. All of the dilutions shown below were created using freshly produced working solutions. By dissolving it in 50 mL of distilled water, sodium NQS 5 mg (0.005 gm) of the reagent was freshly prepared as a stock solution containing 100 ppm. 0.2 M sodium hydroxide is used in this recipe. To make it, dissolve 1.6 gm sodium hydroxide in 25 mL distilled water in a volumetric flask and dilute to 200 mL with more distilled water. 0.2 M potassium chloride is used in this experiment. To make a standard solution, dissolve 2.858 gm in 20 mL distilled water in a volumetric flask and dilute it with distilled water to 200 mL in a volumetric flask. 0.2 M boric acid is used in this recipe. Therefore, it was necessary to prepare a standard solution of 1.2366 gm by dissolving it in 25 mL of distilled water and diluting it to 100 mL in a volumetric flask before using it.
Solution of sodium hydroxide and boric acid as a buffer 50 mL distilled water was used to dissolve the boric acid, which was then combined with 4.15 mL sodium hydroxide (0.2 M) in a 100 mL volumetric flask to form a solution. After that, the solution was diluted with distilled water until it reached the desired concentration.
A pH 10 buffer solution containing boric acid, potassium chloride, and sodium hydrochloride was prepared in a 100 mL volumetric flask using 25 mL of boric acid (0.2 M), 25 mL of potassium chloride (0.2 M), and 21.85 mL of sodium hydroxide (0.2 M), which was then diluted with distilled water to the desired concentration.
Sodium hydroxide and potassium chloride buffer solution with a pH of 12 was prepared by combining 50 mL of potassium chloride (0.2 M) and 24 mL of sodium hydroxide (0.2 M) in a 100 mL volumetric flask and diluted with distilled water to the desired concentration.
Instruments
All flow injection analyses were carried out utilizing a Rheodyne valve 7725, a Rabbit peristaltic pump, a BioLogic QuadTec UV-Vis Detector, and a Sartorius CPA2P Competence Analytical Balance, as well as a Sartorius CPA2P Competence Analytical Balance. G-Chrom V1.5 loop volume is 40 litres for appropriate analytical methods that can be designed and developed for a variety of purposes, such as qualitative analysis, formulation, conservatism content, and estimating analyte concentrations in biological or non-biological fluids. The software designer is responsible for the methods’ scanning, calibration, measurements, and report editing.
A flow injection system model that our laboratory designed and built.
RESULTS
Determine the maximum wavelength (max)
1 mL of a standard solution containing 50 ppm MA was transferred to a 10 mL volumetric flask, followed by 1 mL of buffer solution (pH 12) and 1 mL of NQS solution. Finally, 1 mL of a standard solution containing 50 ppm MA was added (100 ppm). The components were combined and diluted with distilled water to ensure proper mixing.
Result of lambda max
![]() . | ![]() . | ![]() . | |||
---|---|---|---|---|---|
Lambda . | S1 . | Lambda . | S2 . | Lambda . | S3 . |
399 | 0.04 | 474 | 0.127 | 477 | 0.125 |
![]() . | ![]() . | ![]() . | |||
---|---|---|---|---|---|
Lambda . | S1 . | Lambda . | S2 . | Lambda . | S3 . |
399 | 0.04 | 474 | 0.127 | 477 | 0.125 |
Optimization of experimental conditions
To select the best potential experimental conditions for the experiment, a single parameter was adjusted, and the impact on the absorbance of the coloured species was measured.
Result of absorbance
Index . | Sample . | MA ppm . | Peak Height . |
---|---|---|---|
1 | A | 1 | 0.019 |
2 | B | 1 | 0.019 |
3 | C | 5 | 0.064 |
4 | D | 10 | 0.123 |
5 | E | 15 | 0.182 |
6 | F | 20 | 0.238 |
Index . | Sample . | MA ppm . | Peak Height . |
---|---|---|---|
1 | A | 1 | 0.019 |
2 | B | 1 | 0.019 |
3 | C | 5 | 0.064 |
4 | D | 10 | 0.123 |
5 | E | 15 | 0.182 |
6 | F | 20 | 0.238 |
Equation and R-squared value with ideal values of a calibration curve
MA ppm . | Abs . | QR . |
---|---|---|
1 | 0.019 | 0.019 |
1 | 0.019 | 0.019 |
5 | 0.064 | 0.065 |
10 | 0.123 | 0.123 |
15 | 0.182 | 0.181 |
20 | 0.238 | 0.239 |
MA ppm . | Abs . | QR . |
---|---|---|
1 | 0.019 | 0.019 |
1 | 0.019 | 0.019 |
5 | 0.064 | 0.065 |
10 | 0.123 | 0.123 |
15 | 0.182 | 0.181 |
20 | 0.238 | 0.239 |
The influence of flow rate
The following is the effect of the length of the mixing coil
The following is the effect of the base type and the quantity added
Effect of NQS concentration
Repeatability
Dead volume
The determination of dispersion
In aqueous solutions, MA can be determined as follows
Value of sample application
Index . | Taken . | Founded . | Peak Height . |
---|---|---|---|
1 | 9.5 | 9.457 | 0.117 |
2 | 14.5 | 14.767 | 0.178 |
3 | 17.5 | 17.554 | 0.211 |
Index . | Taken . | Founded . | Peak Height . |
---|---|---|---|
1 | 9.5 | 9.457 | 0.117 |
2 | 14.5 | 14.767 | 0.178 |
3 | 17.5 | 17.554 | 0.211 |
DISCUSSION
The technique is based on the physical characteristics of electromagnetic radiation. The study indicated that the simple injection technique could detect drug concentrations in aqueous solutions. According to the findings, the detection limit was determined to be LOD = 0.021 ppm, the limit of quantification was determined to be LOQ = 0.071 ppm, the straight-line equation for drug concentration versus absorption was determined to be y = 0.012 x + 0.007, and the correlation equation for the standard specification 0.9999 linearities was determined to be in the range of 2–20 ppm. The calibration curve findings showed a high correlation coefficient with linearity, showing a strong association between peak height and concentration, which is important to the study's objectives. G-Chrome is APA for this type of analysis. The analysis was conducted based on a single reading. This method is both quick and precise.
Along with the standard deviation (SD) and relative standard deviation (RSD%), this method gave the analyst greater latitude in computing the SD. The data, graphs, and tables were merged into a final, extremely trustworthy report by computing the equations of straight and linear lines without using normal Excel computations. Compared to non-destructive methods and near-infrared spectroscopy, the results from this method are acceptable (NIRS).
MA has no long-term or fatal effects, but it might cause health problems if ingested in excess. MA has been shown to interfere with the anticoagulant activity of aspirin. Some studies have linked anti-inflammatory medications to an increased incidence of stomach ulcers. When used with diuretics, the efficacy of the diuretics is decreased, and the risk of kidney damage increases. The FDA in the United States has ordered a review of all NSAIDs to warn about the potential for kidney issues in newborns. Several techniques are employed in drug detection and identification, including differential pulse polarization, thin layer chromatography, adsorption voltammetry, and differential spectroscopy. The laboratory tests and G-Chrome program are more precise, adaptable, and time-efficient when constructed on measurements. This technique cumulatively records the individual measurements of each sample throughout time. This approach necessitates less analysis time than collecting all of the statistical data necessary to produce the final report. This pattern might be appropriate for indicators. Routine measurements are utilized in spectroscopic analysis to determine flow and injection. In conclusion, the newly developed G-Chrome method is inapplicable to solid samples. On the other hand, solid samples can be dissolved in a solvent tested against G-Chrome.
For future developments, new sensors could be integrated into this technique, such as electromagnetic sensors nanosensors (Shojaei et al. 2016; Ryecroft et al. 2019, 2021; Mohammadian et al. 2022) or membrane sensors (Babakhanian 2012; Noroozi & Keypour 2017).
CONCLUSIONS
A paradigm shift has occurred in the visual evolution of FI-UV. Unlike previous instruments, the new one employs a novel, constructed, in-laboratory planned, and in-laboratory managed G-Chrome flow-injection software to determine the spectroscopic approach. This technology is simple to operate, and data transfer is automated. Because of the internal design of the software used in this approach, injecting a sample and then repeating it at an intersection or altering the sample are simple. Additionally, it was discovered that the data acquired was accurate and equivalent to that produced using more complex instruments. This system distinguishes itself via its low cost and ease of use, high degree of flexibility, precision, and control over the findings, and, most importantly, the analyst's capacity to construct and improve the system and methodology.
For future developments, new sensors could be integrated into this technique, such as electromagnetic or membrane sensors.
DATA AVAILABILITY STATEMENT
Data cannot be made publicly available; readers should contact the corresponding author for details.
CONFLICT OF INTEREST
The authors declare there is no conflict.