A simple, rapid, sensitive reversed-phase high-performance liquid chromatography method was developed and validated for simultaneous measurement of albendazole and praziquantel with an internal standard, simvastatin, at single wavelength of 225 nm. Chromatographic separation was performed on an Enable C 18 column (250 mm × 4.6 mm, 5 m: Spinco Biotech Pvt Ltd) and a mobile phase consisting of acetonitrile:water (60:40, v/v) with 10% orthophosphoric acid to adjust the pH to 3.2, at a flow rate of 1.0 ml/min. The calibration curve was linear (r 2 ≥ 0.999) over the concentration range 0.05-8.0 g/ml. The concentrations of simvastatin was 1.0 g/ml. The limit of quantification was 0.05 g/ml for both albendazole and praziquantel. No interference was found by the excipients in the synthetic mixture. The proposed methods were validated as per International Conference on Harmonisation guidelines for linearity, accuracy, precision and robustness for estimation of albendazole and praziquantel in bulk and in a synthetic mixture, and the results were found to be satisfactory.

A very simplistic, selective, sensitive, and reproducible procedure based on a reversed-phase highperformance liquid chromatography was used and developed for the determination of praziquantel in rat plasma. For the separation of praziquantel from the internal standard, diazepam on an Enable, C18 column (250×4.6 mm, 5 µm particle size), with the retention time of 6.4, 8.5 min, respectively. For praziquantel with UV detector at 225 nm. The mobile phase was a mixture of acetonitrile:water in a ratio of (60:40 v/v), running through the column at the flow rate of 1 ml/min. Sample preparation of 200 µl of plasma was done by a protein precipitation by using perchloric acid. Calibration curve was found to be linear with correlation coefficients (r 2 ) is 0.9989 prepared in plasma at the concentrations of 5 to 1000 ng/ml. The precision of the above method was based on inter-day, and intra-day repeatability, and reproducibility (day-to-day variation) were found to be within the limit of 15%. Limit of quantification was accepted and found to be 5 ng/ml using 200 µl samples. The method appears to be robust and has been applied to a pharmacokinetic study of praziquantel in three groups of rats with a single oral dose of 40 mg/kg body weight.

Retinoid treatment is employed during residual disease treatment in neuroblastoma, where the aim is to induce neural differentiation or death in tumour cells. However, although therapeutically effective, retinoids have only modest benefits and suffer from poor pharmacokinetic properties. In vivo, retinoids induce CYP26 enzyme production in the liver, enhancing their own rapid metabolic clearance, while retinoid resistance in tumour cells themselves is considered to be due in part to increased CYP26 production. Retinoic acid metabolism blocking agents (RAMBAs), which inhibit CYP26 enzymes, can improve retinoic acid (RA) pharmacokinetics in pre-clinical neuroblastoma models. Here, we demonstrate that in cultured neuroblastoma tumour cells, RAMBAs enhance RA action as seen by morphological differentiation, AKT signalling and suppression of MYCN protein. Although active as retinoid enhancers, these RAMBAs are highly hydrophobic and their effective delivery in humans will be very challenging. Here, we demonstrate that such RAMBAs can be loaded efficiently into cationic liposomal particles, where the RAMBAs achieve good bioavailability and activity in cultured tumour cells. This demonstrates the efficacy of RAMBAs in enhancing retinoid signalling in neuroblastoma cells and shows for the first time that liposomal delivery of hydrophobic RAMBAs is a viable approach, providing novel opportunities for their delivery and application in humans.

INTRODUCTIONThe most common helminthic disease of the nervous system is nee is the most common helminthic disease of the nervous system, is neurocysticercosis, which is considered as a serious public health problem in developing countries of Latin America, Asia and Africa [1][2][3]. The use of both the drugs Albendazole [ABZ] and Praziquantel [PRQ] consider an effective against the cystic larvae for the treatment of neurocysticercosis over the last 20 years with the use of both the drugs ABZ & PRQ. ABZ has been found an effective drug of choice than PRQ, but this persistence of cysts even after continuous use of ABZ [2]. For the patients, who were the persistence of cyst after the use of ABZ, an alternative treatment therapy was developed where there was simultaneous use of PRQ and ABZ has been evaluated [4][5]. Albendazole and Praziquantel in combination were used extensively for human hydatid disease [6][7][8][9]. Albendazole [ABZ] is an inactive moiety but it readily gets metabolized to an active metabolite Albendazole sulfoxide [ABZSO] then this ABZSO is then further metabolized to an inactive metabolite Albendazole sulfone [ABZSO2] [10]. As ABZ is metabolized extensively, therefore, the plasma concentration of ABZ is also very low as a result the pharmacokinetic studies were been done using Albendazole sulfoxide [ABZSO] as an active metabolite and Albendazole sulfone [ABZSO2] as an inactive metabolite [11][12][13][14][15]. Metabolism of Praziquantel [PRQ] occurs giving a number of hydroxylated metabolites [16][17][18], among which the active metabolite is mainly trans-4-hydroxypraziquantel [TRANS], an active metabolite [19]. Evaluation and the determination of various pharmacokinetic parameters of ABZ and PRQ, the method has been developed

The precision of the method based on within-day repeatability and reproducibility (day-to-day variation) was within 15% (relative standard deviation: R.S.D. should be less than 15 according to CDER guidance for Bio-analytical Method Validation). Good accuracy was observed for both the intra-day or inter-day assays, as indicated by the minimal deviation of mean values found with measured samples from that of the theoretical values (below ±15%). Limit of Quantitation (LOQ) was

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To develop a quick, simple and reproducible dual column high performance liquid chromatography (HPLC) method to determine the albendazole and its metabolites in rat plasma. Albendazole (ABZ), albendazole sulfoxide (ABZSO) and albendazole sulfone (ABZSO2) were analyzed in rat plasma by high performance liquid chromatography using UV-detector. Preparation of plasma samples was carried out by protein precipitation using 8.25% perchloric acid. This method involves two different mobile phases with two different columns and different wavelengths. Estimation of Albendazole was done using Enable C18 column (250 mm × 4.6 mm, 5μm: SpinCo Biotech Pvt. Ltd.), mobile phase acetonitrile: water in the ratio 60: 40, wavelength 225nm and Praziquantel as an internal standard (IS). The retention time for Albendazole and Praziquantel was 3.7 and 6.4 minutes respectively. But the estimation of Albendazole Sulfoxide, Albendazole Sulfone were done by using Phenomenex C18 Luna column (250 mm × 4.6 mm, 5μm: USA), mobile phase acetonitrile: methanol: phosphate buffer (20mM) in the ratio 20: 25: 55. The pH was adjusted to 6.9 using 0.1N NaOH solution, wavelength 290nm and oxfendazole an internal standard (IS). The retention time for Albendazole Sulfoxide, Albendazole Sulfone, and Oxfendazole was 5.5, 7.0 and 8.2 minutes respectively. Both the methods were validated over the range from 0.005-5µg/mL for Albendazole, 0.05-80µg/mL for Albendazole Sulfoxide and Albendazole Sulfone. Both the method showed % RSD and % DEV lower than 15% for all the analytes. The limit of quantitation was 0.005µg/mL for Albendazole whereas 0.05µg/mL for Albendazole Sulfoxide and Albendazole Sulfone. Metabolites of albendazole were analyzed in rat plasma samples using a single dose of Albendazole 50mg/kg was determined application of this method was also used to found the pharmacokinetic studies.