Analytical Methods for Determination of Ketoprofen Drug: A review

Ketoprofen has recently been proven to offer therapeutic potential in preventing cancers such as colorectal and lung tumors, as well as in treating neurological illnesses. The goal of this review is to show the methods that have been used for determining ketoprofen in pharmaceutical formulations. Precision product quality control is crucial to confirm the composition of the drugs in pharmaceutical use. Several analytical techniques, including chromatographic and spectroscopic methods, have been used for determining ketoprofen in different sample forms such as a tablet, capsule, ampoule, gel, and human plasma. The limit of detection of ketoprofen was 0.1 ng/ ml using liquid chromatography with tandem mass spectrometry, while it was 0.01- 0.30 µg/ ml using high performance liquid chromatography and 0.00004 - 0.436 µg/ ml, 0.82 µg/ ml, 1.0 µg/ ml, 10 µg/ ml and 208.5 - 237.6 µg/ ml using flow injection, electrokinetic chromatography, capillary electrophoresis, gas chromatography-flame ionisation detection and derivative infrared spectroscopy respectively. Doi:


Introduction
Non-steroidal anti-inflammatory drugs (NSAIDs) and their metabolites are widely used in human medicine. Several methods for monitoring the most important members of this pharmacological class in different environmental samples were investigated due to the general problem of drug contamination and environmental risk assessment [1]. In medicine, NSAIDs are routinely used to treat rheumatoid arthritis and osteoarthritis [2].

IHJPAS. 5 3 (3)2022
77 The development of precise and reliable analytical methods for NSAID determination in a variety of samples is critical to employing NSAIDs safely in the pharmaceutical industry and medicinal therapies. These methods gather qualitative and quantitative data on the purity, pharmacokinetics, and pharmacodynamics of a drug, among other things. The metabolites formed as a result of this process can be far more harmful than the initial drug, necessitating drug environmental monitoring [3].
This review focuses on one of the anti-inflammatory drugs, ketoprofen, which is a highly effective medicine that has been utilized in a range of clinical trials and therapies. Ketoprofen is a distinct active ingredient in a multicomponent pharmaceutical form through routine pharmaceutical analysis using numerous chemical methods. Ketoprofen may be used to prevent and treat cancers such as colorectal and lung cancers, as well as neurological illnesses. Several ketoprofen formulations have also been used to treat a wide range of acute and chronic inflammatory diseases. Ketoprofen has been used to treat osteoarthritis, rheumatoid arthritis, menstrual cramps, and ankylosing spondylitis, among other disorders. Figure 1 shows the chemical structure of ketoprofen. Simple, low-cost, and ecologically sound methods should be developed. As one of the important aspects of the analysis, sample preparation should be simple and quick. Because of the intricacy of the samples and the potential influence of interferences, selectivity should be emphasized as well.

Results and Discussion
Although a variety of analytical procedures have been used to determine ketoprofen, highperformance liquid chromatography (HPLC) is the most often used. The results of the method analysis are summarised in Table 1. Ketoprofen was determined in pharmaceutical formulations by Kormosh and co-workers using a simple spectrophotometric method. The procedure involves reacting ketoprofen with
A UV spectrophotometric method was used to analyze ketoprofen in its dose form, with 1M NaHCO3 as the diluent. At 260 nm, ketoprofen had the highest absorption. It was shown to be linear (r 2 =0.998) with low detection and quantification limits (0.78 µg/ml, 2.35 µg/ml) [7].
A simple kinetic method is used to identify ketoprofen in its purest form, medicines, and biological fluids. In the procedure, an electrophilic intermediate was generated, which then reacts with ketoprofen to produce a colored product. The absorbance was measured at 605 nm. The correlation was linear, with a LOD of 0.07 µg/ml. Tablets, gel, and suspension had percent recoveries of 100.11, 100.10, and 100.11, respectively, but suppositories, capsules, and ampoules all had percent recoveries of 100.0 [8].
A flow injection method is coupled with it sensitizing by Zhuang and Song to generate a fast chemiluminescence method to analyse ketoprofen. R 2 and LOD and R.S.D. were determined and found to be of 0.9999, 2.0 × 10 -8 mol/L and 0.8 % respectively [9].
For the identification of ketoprofen in pharmaceutical preparations, a fused silica capillary was employed for separation at 200 nm with 15% (v/v) methanol. It takes roughly 13 minutes to complete a single separation. When comparing the results to those reported in the literature using the RP-HPLC method, no statistically significant differences were detected [10].
Ketoprofen in dialystes was determined using LC-MS/MS on a C18 column (100 mm × 2.1mm i.d., 1.7µm) with a mobile phase of 60:20:20 (v/v/v). 5µl samples were injected and analyzed at a temperature of 22 ± 0.5°C. At 1.07 minutes, ketoprofen eluted. At the transitions 253.00 > 209.00 ketoprofen response was optimized. Calibrations curves showed a good linear correlation with correlation values > 0.999. The precision and accuracy were found to be between 99.97 and 104.67 %, with a mean recovery of ketoprofen of 88.03 ± 0.3 %. The LOD and LOQ were determined to be 0.1 and 0.5 ng/ml, respectively [11].
Rapid and easy analysis of ketoprofen in bodily fluids was developed using HPLC. This antirheumatic medication, as well as an internal standard, must be extracted selectively from acidified plasma and urine using ether. After the ether has evaporated, the residue is dissolved in methanol and examined using RP-HPLC [12].
HPLC was performed to quantify ketoprofen in human plasma using a C18 (100 4.6 mm) column with an acetonitrile/ potassium dihydrogen phosphate 0.01 M (40:60, v/v) mobile phase at pH 3.5. The flow rate was fixed to 5 ml/ min and a wavelength of 254 nm. It took less than 5 minutes to complete the analysis. The RSD was less than 13% at this level with the lowest LOD of 10 ng/ ml. After application of two topical ketoprofen formulations, human plasma samples were taken from healthy volunteers to measure relative bioavailability and demonstrate that ketoprofen applied topically has a low systemic bioavailability [13].
In the study by Azeez and co-workers, a simple first and normal derivative IR spectroscopy method was used for determining ketoprofen in pharmaceutical formulations. Ketoprofen has been quantified in the range of (1000 to 4000)µg/ml using transmittance measurements for the normal and first derivative spectrums against concentrations with a relative error of +4.33% and 4.78%, respectively, and RSD 1.15% and 1.37%. The r 2 coefficients for both techniques were 0.993 and 0.978, respectively. The procedures were used to determine ketoprofen in various pharmaceutical samples, with a recovery rate of 97.691% [14].
The ketoprofen was determined in an oral pharmaceutical formulation by Blanco and coworkers using capillary electrophoresis method. All samples were examined during a stability study revealed that the ketoprofen content in the body did not alter considerably over time. The enantiomeric impurities was ranged from 0.1% to 0.4 % [15].

Conclusion
To determine the quality, safety, and efficacy of ketoprofen medications, as well as to monitor ketoprofen therapy, it is necessary to develop reliable, accurate, and efficient analytical methods. Therefore, the purpose of the current essay was to review the previous studies over the past few decades that have provided important information on determining ketoprofen. Different methods for determining ketoprofen are discussed in this review including chromatographic, spectroscopic and spectrometric methods. Although HPLC and UV spectroscopy was the most commonly used technologies for ketoprofen determination, LC-MS/MS showed great sensitivity with the lowest LOD (0.5 ng/ml). However, to develop and test new inventive ketoprofens, more study is required in this field based on green chemistry principles.