The combination of certain non-sedating antihistamines (NSA) such as fexofenadine (FXD), ketotifen (KET) and loratadine (LOR) with pseudoephedrine (PSE) or acetaminophen (ACE) is widely used in the treatment of allergic rhinitis, conjunctivitis and chronic urticaria. A rapid, simple, selective and precise densitometric method was developed and validated for simultaneous estimation of six synthetic binary mixtures and their pharmaceutical dosage forms. The method employed thin layer chromatography aluminum plates precoated with silica gel G 60 F254 as the stationary phase. The mobile phases chosen for development gave compact bands for the mixtures FXD-PSE (I), KET-PSE (II), LOR-PSE (III), FXD-ACE (IV), KET-ACE (V) and LOR-ACE (VI) [Retardation factor (Rf ) values were (0.20, 0.32), (0.69, 0.34), (0.79, 0.13), (0.36, 0.70), (0.51, 0.30) and (0.76, 0.26), respectively]. Spectrodensitometric scanning integration was performed at 217, 218, 218, 233, 272 and 251 nm for the mixtures I-VI, respectively. The linear regression data for the calibration plots showed an excellent linear relationship. The method was validated for precision, accuracy, robustness and recovery. Limits of detection and quantitation were calculated. Statistical analysis proved that the method is reproducible and selective for the simultaneous estimation of these binary mixtures.

The present study was designed to evaluate the potential protective effects of the cysteinyl leukotriene receptor blocker montelukast (MNK) and the xanthine oxidase inhibitor febuxostat (FBX) and their combination on a model of acute gouty arthritis induced by intraarticular injection of monourate sodium crystal (MUC) injection in rats. Additionally, we established an HPTLC method for the quantitative determination of both drugs simultaneously and applied this method to detect this combination in rat plasma. In this study, the treated male Wistar rats were grouped as follows: a negative control group injected with phosphate buffer saline (PBS) and a positive control group injected with MUC in their tibiotarsal joint. Four groups were treated orally with diclofenac (4 mg kg-1), MNK (10 mg kg-1), FBX (5 mg kg-1) and MNK plus FBX before MUC injection in their tibiotarsal joints. MUC injection in joints without pretreatment led to a progressive significant increase in joint diameter and heavy leucocytic infiltration compared to the PBS-injected joints. Treatment with diclofenac or a combination of MNK and FBX significantly decreased both joint diameters and leucocytic infiltration compared to the MUC group. MNK or FBX treatment attenuated leucocytic infiltration and significantly decreased joint diameters compared to the MUC group. Thus, MNK and FBX can prevent the development of MUC-induced acute gouty arthritis in rats. Also, MNK can be an alternative preventive treatment, particularly in elderly patients who cannot tolerate NSAIDs or corticosteroid. Furthermore, a new thin-layer chromatographic method combined with fluorescence detection was developed and validated for the simultaneous estimation of a mixture of FBX and MNK in spiked human plasma. In this method, we employed TLC aluminium plates precoated with silica gel G 60F254 as the stationary phase and chloroform : methanol (9 : 1, v/v) as the mobile phase. The optimized mobile phase selected for development gives compact bands (Rf values are 0.28 and 0.63 for FBX and MNK, respectively). The emission intensities were measured using a K400 optical filter after excitation at 322 nm. The linear regression data for the calibration plots showed excellent linear relationship (r = 0.9990 and 0.9996 for FBX and MNK, respectively), and the linearity range was 10.0-800.0 ng per band for both drugs. According to ICH-guidelines, this method was validated for precision, accuracy, robustness and selectivity. Also, the limits of detection and quantitation were calculated. In addition, stability studies on the studied mixture were performed. Statistical analysis proved that this method is reproducible and selective for the estimation of a mixture of FBX and MNK.

A validated simple, novel, and rapid spectrofluorimetric method was developed for the determination of some non-sedating antihistamines (NSAs); namely cetirizine (CTZ), ebastine (EBS), fexofenadine (FXD), and loratadine (LOR). The method is based on measuring the native fluorescence of the cited drugs after protonation in acidic media and studying their quantitative fluorescence intensity - structure relationships. There was a linear relationship between the relative fluorescence intensity and the concentration of the investigated drug. Under the optimal conditions, the linear ranges of calibration curves for the determination of the studied NSAs were 0.10-2.0, 0.20-6.0, and 0.02-1.0 [Formula: see text] for (CTZ, FXD), (EBS), and (LOR); respectively. The factors affecting the protonation of the studied drugs were carefully studied and optimized. The method was validated according to ICH guidelines. The suggested method is applicable for the determination of the four investigated drugs in bulk and pharmaceutical dosage forms with excellent recoveries (97.67-103.80%). Quantitative relationships were found between the relative fluorescence intensities of the protonated drugs and their physicochemical parameters namely: the pKa, log P, connectivity indexes (χ(v)) and their squares. Regression equations (76) were obtained and not previously reported. Six of these equations were highly significant and used for the prediction of RFI of the studied NSAs.

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An innovative, simple, fast, specific and sensitive high performance liquid chromatographic method with Ultraviolet detection (HPLC/UV) was established and validated for simultaneous determination of a combination of three commonly prescribed antigout drugs namely; Colchicine (CLN), Probenecid (PRD) and Febuxostat (FBX) in dosage forms and in human urine samples. GraceSmart RP C18 column was utilized for separation of the studied mixture using isocratic mode of mobile system consisting of acetonitrile: water (55: 45, v/v; containing 0.5% v/v formic acid). Flow rate and detection wavelengths programming were designed to obtain rapid and efficient separation. The cited drugs were separated within less than 9 minutes. The retention times (tR) were 3.597, 5.357 and 8.250 for CLN, PRD and FBX; respectively. The linearity range for all the investigated drugs was 0.040 -50.0 µg/mL with detection limits of 1.94 -6.48 ng/mL. Additionally, the developed method was validated according to ICH and US-FDA guidelines and was successfully applied for simultaneous estimation of the studied drugs in their pure form, and in laboratory-made tablets mixture. The proposed method was also used for analysis of CLN and PRD in their combined tablets and in human urine samples obtained from healthy volunteers with good recoveries (98.39-101.87%). Furthermore, the stability of CLN-PRD mixture in urine samples was studied. This method is suitable for quality control purposes for simultaneous analysis of these co-administered antigout agents in their binary and ternary mixtures.

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