Abstract

Etoricoxib is a selective COX-2 inhibitor. The way non-steroidal anti-inflammatory drugs (NSAIDs) function is by blocking the COX enzyme, which is an inflammatory mediator. Osteoarthritis, rheumatoid arthritis, and primary dysmenorrhea are all treated with etoricoxib. Therefore, the main objective of this work is to examine etoricoxib in pharmaceutical and biological formulations using both qualitative and quantitative methods. In this review paper, we have compiled the methodologies for estimating etoricoxib based on liquid chromatography-mass spectroscopy (LC-MS), high-performance liquid chromatography (HPLC), and UV/Vis spectroscopy. Furthermore, we have discussed the bioanalytical methods for ETX analysis. To sum up, this review article will assist researchers in developing new methods for estimating drug concentrations in biological fluids and pharmaceutical dose forms.

Keywords

Introduction

Rheumatoid arthritis pain and inflammation are frequently managed using non-steroidal anti-inflammatory medications (NSAIDs). Their suppression of cyclooxygenase (COX) enzymes, which convert arachidonic acid into prostaglandins, is responsible for their analgesic and anti-inflammatory properties as well as part of their chemopreventive actions.(1) Etoricoxib, 5-chloro-3-(4-methanesulfonylphenyl)-6-methyl-[2,3]-bipyridinyl is a highly selective cyclooxygenase–2 (COX-2) inhibitor.(2) The two types of the enzyme are cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX-1 regulates normal physiological prostaglandin-mediated functions such gastric cytoprotection and platelet aggregation. Nonselective NSAIDs' suppression of COX-1 has been connected to both platelet inhibition and gastric injury. It is well known that prostanoid mediators of pain and inflammation are produced in large part by COX-2.(2) Etoricoxib is used to treat osteoarthritis, rheumatoid arthritis, chronic low back pain, acute pain, dysmenorrheal, acute gouty arthritis and ankylosing spondylitis.(3)

Figure 1: Chemical Structure of Etoricoxib

Mechanism of Action :

One possible explanation for the anti-inflammatory, analgesic, and antipyretic effects of NSAIDs is the inhibition of prostaglandin synthesis. The exact mechanism of action is yet unknown, but it appears that these effects are produced by blocking the COX-2 isoenzyme at the sites of inflammation, which in turn causes a reduction in the production of several prostaglandins from their precursors, arachidonic acid. Etoricoxib particularly inhibits the COX-2 enzyme, which is essential for the control of pain and inflammation. In contrast to non-selective NSAIDs, it does not stop platelet aggregation. Moreover, affinity for COX-1 is minimal to nonexistent.(4)

Pharmacokinetics :

Absorption :

Bioavailability is 100% following oral administration.(4)

Protein binding :

92%(4)

Metabolism :

Hepatic, primarily via CYP3A4. (4)

Pharmacodynamics :

Etoricoxib is a COX-2 selective inhibitor (approximately 106 times more selective for COX-2 inhibition over COX-1). (4)

Analytical Account of ETX

An extensive literature search revealed a variety of analytical methods, including UV/Visible Spectrophotometry, HPLC, HPTLC, UPLC, LC-MS/MS, and bioanalytical approaches, for the determination of RFX in bulk and pharmaceutical formulations. Celecoxib (CXB), Paracetamol (PCT), Salicylic acid (SCA), Ketoprofen (KPF), Nimesulide (NMS), Riluzole (RLZ), Drotraverine (DRT), Thiocholchicoside (THC), Pregabalin (PGBN), Tolperisone (TOP) are all evaluated alone as well as in conjunction with ETX.

Figure 2 shows different analytical methods implemented for the estimation of ETX

Bio-analytical method for ETX

A branch of analytical chemistry known as "bio-analysis" deals with the quantitative measurement of biotics (macromolecules, proteins, DNA, large-molecule drugs, metabolites) and xenobiotics (drugs and their metabolites) in biological systems. The summary of the reported bioanalytical methods is shown in Table 1

Table 1: Bioanalytical determination of ETX

*** Not Provided

UV-Visible spectroscopy method for ETX

The spectrophotometric methods have been accounted for the determination of ETX. The details of Spectrophotometry determination of basic principle, sample matrix, lambda max, solvent linearity range and the correlation coefficient are summarized in Table 2.

Table 2: Spectrophotometric methods used for determination of ETX

*** Not Provided

Liquid-Chromatography-Mass Spectroscopy methods (LC-MS) for ETX:

In recent years, the combination of LC/MS has gained a lot of attention for the analysis of interest analytes in complex samples with improved performance. In brief, after a thorough examination, LC/MS interfaces are divided into two categories namely interfaces for indirect and direct input of column effluent. A mechanical mechanism is employed to transmit the column effluent to the MS vacuum at an indirect introduction interface. A classic example of an indirect introduction type of interface is the transportation system. In the case of the direct introduction system, the column effluent flows directly into the mass spectrometric vacuum system via a tube. Mainly, the most straightforward method of linking LC and MS appears to be the direct introduction. In this section, we have discussed the LC-MS methods for the determination of ETX in a dosage form Table 3.

Table 3. Summary of LC-MS methods for the determination of ETX in a dosage form

HPLC method for ETX

The specificity of the HPLC method is excellent and simultaneously sufficient precision is also attainable. However, it has to be stated that the astonishing specificity, precision, and accuracy are attainable only if wide-ranging system suitability tests are carried before the HPLC analysis. For this reason, the expense to be paid for the high specificity, precision, and accuracy is also high. The summary of the reported HPLC methods is shown in Table 4.

Table 4: Summary of HPLC methods for the determination of ETX in a single and combined dosage form

HPTLC method for ETX

Thin-layer chromatography is a popular technique for the analysis of a wide variety of organic and inorganic materials, because of its distinctive advantages such as minimal sample clean-up, a wide choice of mobile phases, flexibility in sample distinction, high sample loading capacity and low cost. The summary of the reported HPTLC methods is shown in Table 5.

Table 5: Summary of HPTLC methods for the determination of ETX in a single and combined dosage form

 UPLC methods for ETX

Ultra-performance liquid chromatography (UPLC) is a new category of separation based on well-established principles of liquid chromatography, which utilizes sub-2-mm particles for the stationary phase. The developed UPLC method is validated and therefore could be further used for quantitative analysis of Etoricoxib. Sanjay Shesha Shetgar, Ramadevi Dharmasoth, Bandlamudi Mallikarjuna Rao, Basavaiah Keloth established UPLC method development and validation for simultaneous estimation of Etoricoxib and Thiocolchicoside in tablets. UPLC was carried out in Hibar, C18 column of dimension 100 × 2.1 mm, 1.8 ?m,at 30°C, by using  mobile phase 0.1% orthophosphoric acid (pH 2.5) and acetonitrile in a ratio of 90:10 (v/v). The column effluents were monitored at 256 nm using a Acquity Tunable UV detector at a flow rate of 0.3 ml/minute. The linearity of the calibration curve ranged from 1–6 ?g/ml of Thiocolchicoside and 15–90?g/ml of Etoricoxib and the regression coefficient (r2) was 0.999 for both Etoricoxib and Thiocolchicoside drugs.(53)

CONCLUSION

The current review article offers a thorough understanding of the many analytical and bioanalytical techniques both singular and combined developed for etoricoxib. Numerous novel analytical techniques, including as UV spectroscopy, UPLC, HPLC, and HPTLC, have been published for analysis purposes. The method has been tabulated and includes information regarding the mobile phase, stationary phase, retention time, etc. for the researchers' convenience. Future analytical techniques for the bio-analysis of etoricoxib in pharmacological and biological formulations can be developed using the information acquired. In conclusion, it offers an opportunity to gain additional insight into past achievements and prospective future initiatives and modifications aimed at expanding our understanding of etoricoxib.

CONFLICT OF INTEREST

The authors declare that no conflict of interest

ABBREVIATIONS

1. UV/VIS – Ultra violet/visible spectroscopy
2. HPLC – High-performance liquid chromatography
3. HPTLC – High-performance thin layer chromatography
4. LC-MS/MS – Liquid chromatography-mass spectroscopy-mass spectroscopy
5. UPLC – Ultra performance liquid chromatograpy
6. RP – Reverse phase
7. nm – Nanometer
8. ?g/mL – Micro gram per Milliliter
9. PDA - Photo diode array
10. VDX – Valdecoxib
11. SCA – Salicylic acid
12. KPF – Ketoprofen
13. NMS – Nimesulide
14. CXB – Celecoxib
15. RLZ – Riluzole
16. DRT – Drotraverine
17. THC – Thiocholchicoside
18. PCT – Paracetamol
19. PGBN – Pregabalin
20. TOP – Tolperisone

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