Simultaneous Determination of Clidinium Bromide and Chlordiazepoxide in Combined Dosage Forms by High-Performance Liquid Chromatography
A sensitive and precise RP-HPLC method has been developed for the simultaneous estimation of clidinium bromide (CDB) and chlordiazepoxide (CDZ) in pure and pharmaceutical formulations. The separation was achieved on a Nucleodur C8 (250 × 4.6 mm i.d., 5 μm particle size) column at 25°C. CH3CN-MeOH-NH4OAc 0.1M (30 : 40 : 30, v/v/v) was used as the mobile phase at a flow rate of 1.0 mL min−1 and detector wavelength at 218 nm. Almotriptan (ALT) was used as internal standard. The validation of the proposed method was carried out for linearity, accuracy, precision, LOD, LOQ, and robustness. The method showed good linearity in the ranges of 2.5–300.0 and 3.0–500.0 μg mL−1 for CDB and CDZ, respectively. The percentage recovery obtained for CDB and CDZ was 100.40–103.38 and 99.98–105.59%, respectively. LOD and LOQ were 0.088 and 0.294 μg mL−1 for CDB and 0.121 and 0.403 μg mL−1 for CDZ, respectively. The proposed method was successfully applied to the determination of CDB and CDZ in combined dosage forms and the results tallied well with the label claim.
A Novel Validated Analytical Method Development for the Binary Mixture of Mebeverine and Chlordiazepoxide in Pharmaceutical Formulation and its Application to Stress Studies
Purpose: A Stability indicating RP-HPLC method for the determination of Mebeverine and Chlordiazepoxide in bulk and pharmaceutical dosage form was developed and validated. Two methods are available for the determination of this combination and it is required to develop the novel method with cost effective, time consuming, with good sensitivity and less retention time and to know the interference of degradation products which can be performed in the routine analysis. Methods: Stability indicating RP-HPLC method with chromatographic conditions include Agilent C18 column (250 mm×4.6 mm i.d., 5 μ particle size) and the mobile phase consists of 40:60v/v ratio of Methanol and Tri ethyl amine buffer pH 7.0 with OPA at a flow rate of 1.0ml/min at a ambient temperature and the injection volume was 20 μL. Results: Quantification was achieved at 262 nm wavelength using UV detector and the retention times of Mebeverine and Chlordiazepoxide were found to be 3.40 and 7.45 mins. The developed method shows linearity in the range 27- 216 μg/mL for Mebeverine and 1.8-7.4 μg/mL for Chlordiazepoxide. The LOD and LOQ values for Mebeverine were 2.2 μg/mL and 6.5 μg/mL, for Chlordiazepoxide 0.01 μg/ml and 0.03 μg/ml respectively. The regression coefficient for both drugs was found to be 0.999. The mean recoveries ranged from 99.99-100.004% and 99.97-100.01% for Chlordiazepoxide and Mebeverine respectively. The stability study results show that the method for the determination of both the drugs was stable. The percentage degradation for Mebeverine and Chlordiazepoxide were within the limit that is less than 30. Conclusion: Both drugs were eluted with less retention times. Stability was performed which shows that the proposed method was stable. Degradation products were not interfered with the pure drugs of Mebeverine and Chlordiazepoxide. By the stress study the degradation pathways are studied. Hence the developed method was considered as the stability indicating method. The proposed method was performed based on the ICH guidelines.
Synthesis of 2,4-dideoxy-.beta.-D-erythro-hexopyranosyl nucleosides
The synthesis of 1-(2,4-dideoxy-β-D-erythro-hexopyranosyl)thymine (12) 1 was accomplished using two different synthetic routes. It was obtained starting either from 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose or from tri-O-acetyl-D-glucal. The other modified nucleosides, with either a cytosine, guanine, or adenine moiety, were synthesized using the second reaction scheme. Deoxygenation reactions were accomplished with the (2,4-dichlorophenoxy)thiocarbonyl derivatives generated in situ