Introduction
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain and inflammation in rheumatoid arthritis. Their analgesic and anti-inflammatory effects, as well as some of their chemo preventive effects, are attributed to their inhibition of cyclooxygenase (COX) enzymes, which turn arachidonic acid into prostaglandins.1 Rofecoxib is chemically 3-phenyl-4-(p-methylsulphonyl)-phenyl-(5H)-furan–2-one is a highly selective cyclooxygenase–2 (COX-2) inhibitor.2 Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are the two types of the enzyme. Normal physiological processes mediated by prostaglandins, such as platelet aggregation and gastric cytoprotection, are controlled by COX-1. Gastric damage and platelet inhibition have been linked to nonselective NSAID’s COX-1 inhibition. It has been established that COX-2 plays a key role in the production of prostanoid mediators of pain and inflammation.2
In addition to treating acute migraine episodes with or without auras, rofecoxib is also used to treat adult cases of primary dysmenorrhea, rheumatoid arthritis, osteoarthritis, and acute pain.3
Mechanism of Action
The suppression of prostaglandin production appears to be the cause of the anti-inflammatory, analgesic and antipyretic actions of NSAIDs. These effects appear to be achieved by inhibiting the COX-2 isoenzyme at the sites of inflammation, which then results in a decrease in the manufacture of certain prostaglandins from their arachidonic acid precursors, however the precise mechanism of action has not yet been established. The COX-2 enzyme, which is crucial for the regulation of pain and inflammation, is specifically inhibited by rofecoxib. Rofecoxib does not prevent platelet aggregation, unlike non-selective NSAIDs. Affinity for COX-1 is also negligible to non-existent.4, 5
Pharmacokinetics
Absorption: At clinically advised dosages of 12.5, 25, and 50 mg respectively rofecoxib had a mean oral bioavailability of 93%. 4
Protein binding: 87%
Metabolism: Rofecoxib is predominantly metabolized by cytosolic enzymes by reduction. The cis-dihydro and trans-dihydro derivatives of rofecoxib, which make up about 56% of the radioactivity collected in the urine, are the main metabolic products. 8.8% more of the dosage was recovered as the hydroxy derivative's glucuronide, which is a by-product of oxidative metabolism. In humans, rofecoxib's biotransformation into this metabolite can be partially reversed (5%). As COX-1 or COX-2 inhibitors, these metabolites are ineffective. Cytochrome P450 has a small impact on how rofecoxib is metabolized. 4
Pharmacodynamics: In contrast to celecoxib, rofecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism. Like other NSAIDs, rofecoxib exhibits anti-inflammatory, analgesic, and antipyretic activity. NSAIDs appear to inhibit prostaglandin synthesis by inhibiting cyclooxygenase (COX), which is responsible for catalyzing the formation of prostanoids.4
Analytical Account of RFX
An extensive literature search revealed a variety of analytical methods, including UV/Visible Spectrophotometry, High-performance liquid chromatography (HPLC), High-performance thin layer chromatography (HPTLC), Liquid chromatography-mass spectrometry (LC-MS) and bioanalytical approaches, for the determination of RFX in bulk and pharmaceutical formulations. Celecoxib (CXB), Paracetamol (PCT), Diclofenac (DIC), Niflumic Acid (NIF), Mosapride Citrate (MSPC), and Tizanidine (TNZ) are all evaluated alone as well as in combination with RFX.
Figure 2
Different analytical methods implemented for the estimation of RFX in a bulk and pharmaceutical dosage form
Bio-analytical method for RFX
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. 6 The summary of the reported bioanalytical methods is shown in Table 1.
Table 1
Summary of bioanalytical methods for the determination of RFX in a single and combined dosage form
UV-Visible spectroscopy method for RFX
The spectrophotometric methods have been accounted for the determination of RFX. 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 RFX in a single and combined dosage form
Liquid-Chromatography-Mass Spectroscopy Methods (LC-MS) for RFX
The LC/MS combo has drawn a lot of attention recently for its enhanced performance in the detection of important analytes in challenging samples.21, 22, 23 A detailed analysis resulted in the separation of LC/MS interfaces into two categories: interfaces for indirect and direct input of column effluent. The column effluent is transferred mechanically from the indirect introduction contact to the MS vacuum. The transportation system is a prime example of an indirect introduction type of interface. The mass spectrometric vacuum system receives the column effluent directly through a tube in the direct introduction system. In general, the direct introduction seems to be the easiest way to connect LC and MS. 24 In this section, we have discussed the LC-MS methods for the determination of RFX in a dosage form Table 3.
Table 3
Summary of LC-MS methods for the determination of RFX in a single and combined dosage form
|
Sr. No |
Drug |
Matrix |
Stationary Phase |
Mobile Phase |
Internal Standard |
Linearity (mg/mL) |
Ref. |
|
1 |
RFX |
*** |
Shimpak ods C 20 column |
Acetonitrile/0.05% phosphoric acid (35:65) |
*** |
2–36 mg/ml |
|
|
2 |
RFX |
Bulk and pharmaceutical dosage forms |
Symmetry C18 analytical Column |
Acetonitrile-water (50:50, v/v) |
Chlorophenyl methyl sulphone |
125 to 500 mg/ml |
|
|
3 |
TZN and RFX |
Tablets |
Spherisorb ODS column |
Triethylamine (pH adjusted to 2.5 using dilute orthophosphoric acid): acetonitrile 55:45% (v/v) |
Nimesulide |
0.1–0.5 mg/ml 1.2–6.0 mg/ml |
High-performance liquid chromatography (HPLC) method for RFX
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
4. Summary of HPLC methods for the determination of RFX in a single and combined dosage form
High-performance thin layer chromatography (HPTLC) method for RFX
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 RFX in a single and combined dosage form
Conclusion
The current review paper provides in-depth knowledge of the several analytical and bioanalytical methods developed for Rofecoxib, both individually and in combination. For analysis purposes, a variety of unique analytical procedures, including HPLC, HPTLC, LC-MS and UV spectroscopy, etc., have been reported. For the advantage of the researchers, the approach has been laid out in tabular form and includes details about the mobile phase, stationary phase, retention time, etc. The gathered information can be used to create future analytical methods for the bio-analysis of rofecoxib in pharmaceutical and biological formulations. Finally, it provides a chance to learn more about what has previously been accomplished as well as potential future plans and adjustments to further our knowledge of rofecoxib.
Abbreviations
UV/VIS - Ultra violet/visible spectroscopy
HPLC - High-performance liquid chromatography
HPTLC - High-performance thin layer chromatography
LC-MS - Liquid chromatography-mass spectroscopy
RP - Reverse phase
nm - Nanometer
μg/mL - Micro gram per Milliliter
PDA - Photo diode array
CXB – Celecoxib
RFX – Rofecoxib
DIC – Diclofenac
NIF – Niflumic Acid
MSPC – Mosapride Citrate
TNZ – Tizanidine
PCT – Paracetamol
