Abstract
An efficient analytical method for the simultaneous determination of leflunomideand non steroidal anti-inflammatory drugs in API and formulations by LC-UV has been developed. The analytes were separated on Purospher Star, C18 (5 μm, 250×4.6 mm) column at ambient temperature with methanol: water (80:20, v/v, pH at 2.7) at flow rate of 1.5 mL min-1. Experiment was conducted in two phases. Leflunomide was separated with flurbiprofenand ibuprofen (phase- I) and diclofenac sodium and mefenamic acid (phase II). Calibration curves were linear over the range 0.625–5 μg mL-1 in both phases for leflunomide while for flurbiprofen, ibuprofen, diclofenac sodium, mefenamic acid linearity were achieved in the range of 0.625-5, 11.25-90, 1.56-50 and 0.78-25 μg mL-1, respectively with r2>0.9998. Intraday variation was <1.2 and <1.4 %, while in inter-day ranged between 0.042-1.45% and 0.08-1.27% in phase-I and II, respectively. Mean recovery values for intra-day ranged from 99.04-100.4% and 98.48-100.2% and for inter-day were between 98.54-100.29% and 98.85-100.54% in phase-I and II, respectively. The LLOD of leflunomide was 13 ng mL-1, while LLOQ was 39ng mL-1, respectively. LLOD and LLOQ for flurbiprofen, ibuprofen, diclofenac sodium and mefenamic acid were 6.9, 296, 71 and 1.2 ng mL-1 and 21, 897, 214.3 and 3.676 ng mL-1, respectively. Present study showed that nanogram quantities of all the compounds can be estimated accurately. The newly established method was successfully applied to study in vitro interactions between leflunomide and NSAIDs.
Highlights
Leflunomide (Figure 1), 5-methyl-N-[4-(trifluoromethyl) phenyl]isoxazole-4-carboxamide is a leading disease modifying anti-rheumatic drug (DMARD) to treat rheumatoid arthritis (RA) [1]
No liquid chromatographic method has yet been reported for separation and simultaneous analysis of leflunomide along with more than one NSAID these drugs are co-administered simultaneously, so we have developed a simple, reliable, accurate, sensitive, cost effective and least time consuming method suitable for the simultaneous analysis of leflunomide and NSAIDs in API and pharmaceutical formulations
A facile reversed-phase HPLC-UV method for the simultaneous determination of leflunomide, flurbiprofen, ibuprofen, diclofenac sodium and mefenamic acid been developed for the first time
Summary
Leflunomide (Figure 1), 5-methyl-N-[4-(trifluoromethyl) phenyl]isoxazole-4-carboxamide is a leading disease modifying anti-rheumatic drug (DMARD) to treat rheumatoid arthritis (RA) [1]. Leflunomide has a long half-life (11 to 16 d) in humans, and because of this its clinical development has been restricted to use in patients of rheumatoid arthritis [2]. In phase II and III clinical trials of active rheumatoid arthritis, leflunomide was shown to improve primary and secondary outcome measures with a satisfactory safety profile. Continuing research indicates that A77 1726 may down regulate the glycosylation of adhesion molecules, effectively reducing cell-cell contact activation during inflammation [3]. It inhibits T-lymphocyte proliferation after converting to its active metabolite i.e. A771726 in human to produce its anti-arthritic action [4,5,6]
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