APPLICATION OF LIQUID CHROMATOGRAPHY COUPLED WITH MASS SPECTROMETRY IN THE IMPURITY PROFILING OF DRUG SUBSTANCES AND PRODUCTS

As the drug safety and efficacy is hampered in the presence of an impurity, the international regulatory agencies laid down stringent limits for the control of impurities in the active pharmaceutical ingredient and pharmaceutical formulations. The conventional approaches lack the characterization of impurities in trace levels, due to sensitivity issues, hyphenated techniques are preferred. Among the modern hyphenated techniques, liquid chromatography-mass spectrometry (LC-MS) has high sensitivity and can analyze large number of organic compounds in a short period of time. In the present study, the impurity profiling of various drug substances and products using LC-MS about past 6 years were retrospect for its importance, instrumentations, and applications

Colorimetric Determination of Cefadroxil and Ceftriazone in Pharmaceutical Dosage Forms

Purpose: To develop a simple, rapid and selective method for the spectrophotometric determination of cefadroxil and ceftriaxone using 1, 2- napthaquinone-4- sulfonic acid sodium.Methods: The method was based on the derivatization of cefadroxil and ceftriaxone with 1, 2-naphthaquinone-4- sulfonic acid sodium in alkaline medium to yield orange-colored products.Results: The reaction products of cefadroxil and ceftriaxone at their respective max of 475 and 480 nm showed linearity in the concentration range of 10 - 100 and 25 - 175 ìg/ml, respectively. Relative standard deviations of 0.82 % for cefadroxil and 0.95 % for ceftriaxone were obtained. Recoveries of cefadroxil tablets and ceftriaxone injection were in the range of 100.66 ± 0.98 and 99.38 ± 0.84 %, respectively.Conclusion: Recovery studies gave satisfactory results indicating that none of the major additives/excipients interfered with the assay method. Therefore, the proposed method is simple, rapid, precise and convenient for the assay of cefadroxil and ceftriaxone in commercial preparations

DETERMINATION OF OCTANOL-WATER PARTITION COEFFICIENT OF NOVEL COUMARIN BASED ANTICANCER COMPOUNDS BY REVERSED-PHASE ULTRA-FAST LIQUID CHROMATOGRAPHY

Objective: The present study aims at the development of a reversed phase ultra-fast liquid chromatography (RP-UFLC) method for measurement of the lipophilicity (log P) between n-octanol and water for the newly synthesized coumarin derivatives in our laboratory.Methods: The synthesized compounds were dissolved in methanol and analyzed using XTerra RP18 column as the stationary phase and a mixture of methanol (0.25% v/v octanol) and buffer as the mobile phase with isocratic elution.Results: In this study we concentrated on the relationship between a reversed-phase ultra-fast liquid chromatography (RP-UFLC) retention parameters and log P of our synthesized compounds. Furthermore, a good correlation and very close values were obtained between the experimentally determined log P values and values obtained from Chemdraw.Conclusion: The developed method was found to be insensitive to any of the impurities present and moreover it requires very little sample for analysis

DESIGNING OF COUMARIN DERIVATIVES AS SQUALENE SYNTHASE INHIBITORS

Objective: The importance of this research work is to design a library of novel coumarin derivatives by docking evaluation of the designed coumarin derivatives as squalene synthase inhibitor.Methods: The three-dimensional structure of designed molecules of squalene synthase inhibitors was collected from Protein Data Bank. The designed molecules were docked onto the enzymes that are squalene synthase inhibitor - 3WCM, 3WCJ, and 3Q2Z protein using SYBYL-X 2.1. Using a standard protocol, the protein was subjected to minimization and protomol generation.Results: By this method, we visualized the possible binding and also estimated the protein interactions with our intended coumarin library, using SYBYL-X 2.1 software. Into the active site of the selected enzymes, all the 20 coumarins were docked and then the docking scores revealed that the compounds possess high affinity toward the selected enzymes.Conclusion: With the help of virtual evaluation, we have elaborated a fast synthetically accessible coumarin-based compounds, and it is an advanced and original scaffold in the area of probable human squalene synthase inhibitors. Some of the developed compounds show better binding property than ligand, and in 3q2Z, the compound 5d shows better binding property than the protein. Furthermore, 6g and 6c have good binding property. In 3 WCM, the compound 6f has better property. In 3 WCJ, the compounds 6g and 6f show better binding property than the protein

Simultaneous Determination of Ciprofloxacin and Tinidazole in Tablet Dosage Form by Reverse Phase High Performance Liquid Chromatography

Purpose: To develop a simple, sensitive and specific liquid chromatographic method with PDA detection for the simultaneous estimation of ciprofloxacin and tinidazole in tablet dosage form.Methods: Separation was achieved with an Agilent XDB C18, 250 × 4.60 mm 5 μ column, low pressure gradient mode with a ambient temperature and mobile phase comprising acetonitrile water containing 0.1 % orthophosphoric (20:80). The flow rate was 1 ml/min and eluent was monitored spectrophotometrically at 316 nm.Results: The selected chromatographic conditions effectively separated ciprofloxacin and tinidazole with retention time of 3.036 and 4.224 min, respectively. Linearity for ciprofloxacin and tinidazole was in the range 50 - 100 and 60 - 120 μg/ml, respectively. Regression coefficient was 0.999 for both ciprofloxain and tinidazole while recovery waas 100.19 - 100.92 and 99.36 - 100.48 % for ciprofloxacinand tinidazole, respectively. Relative standard deviation (RSD) of intra- and inter-day precision was < 2% for both drugs.Conclusion: The developed method is precise, accurate, reproducible and specific and it can also be used for routine simultaneous quality-control analysis of ciprofloxacin and tinidazole in combination tablets.Keywords: High performance liquid chromatography, Ciprofloxacin, Tinidazole, Simultaneous determination

NOVEL SPECTROPHOTOMETRIC METHODS FOR THE QUANTIFICATION OF DESVENLAFAXINE IN PURE AND PHARMACEUTICAL DOSAGE FORM

 Objectives: Two simple, sensitive and economic spectrophotometric methods are developed for the determination of desvenlafaxine in pure and itspharmaceutical formulations.Methods: The developed methods are based upon the reaction of oxidative coupling of desvenlafaxine with 3-methyl-2-benzthiazolinonehydrazone(MBTH) (Method A) and 2, 2' bipyridyl (Method B) in the presence of ferric chloride. The colored complex produced was measured at 663 nm,522 nm for method A and B respectively against the reagent blank. The optimum experimental parameters for the color productions areselected.Results: Beer's law is valid within a concentration range of 20-100 μg/ml and 5-25 μg/ml and for method A, B respectively. The percentage recoverieswere found in the range of 99.47±0.1789 for method A and 100.08±0.144 for method B. The limit of detection and limit of quantification were foundto be 0.825 μg/ml and 2.5 μg/ml respectively for method A and 0.1061 μg/ml and 0.321 μg/ml for method B respectively.Conclusion: The developed methods are applied for the determination of desvenlafaxine in bulk and its pharmaceutical formulations without anyinterference from excipients.Keywords: Spectrophotometric, Desvenlafaxine, Oxidative coupling, 3-methyl-2-benzthiazolinone hydrazone, 2, 2- bipyridyl, FeCl3

DEVELOPMENT AND VALIDATION OF ZERO AND FIRST ORDER SPECTROPHOTOMETRIC METHOD FOR DETERMINATION OF OPIPRAMOL IN BULK AND PHARMACEUTICAL DOSAGE FORM

Objective: Two simple, precise and accurate zero and first order spectrophotometric methods were developed and validated for the quantification of opipramol in bulk and tablet dosage form.Methods: The quantitative analysis of the drug was carried out using the zero order and first order derivative values were measured at 254 nm and 266 nm respectively. The estimation of the drug was carried out by regression equations with the standard solution.Results: Calibration graph was found to be linear r2 = 0.996 for zero order and r2 = 0.998 for first order derivative over the concentration range of 2-10 µg/ml. Precise (intra-day relative standard deviation [RSD] and inter-day RSD values < 1.0%), accurate (mean recovery = 100.77 %), specific and robust. No obstruction was observed from general pharmaceutical adjutants.Conclusion: The developed derivative methods can be utilized in its routine analysis opipramol in quality control division.Â

Colorimetric Determination of Cefadroxil and Ceftriazone in Pharmaceutical Dosage Forms

Purpose: To develop a simple, rapid and selective method for the spectrophotometric determination of cefadroxil and ceftriaxone using 1, 2-napthaquinone-4-sulfonic acid sodium. Methods: The method was based on the derivatization of cefadroxil and ceftriaxone with 1, 2naphthaquinone-4-sulfonic acid sodium in alkaline medium to yield orange-colored products. Results: The reaction products of cefadroxil and ceftriaxone at their respective λ max of 475 and 480 nm showed linearity in the concentration range of 10 -100 and 25 -175 µg/ml, respectively. Relative standard deviations of 0.82 % for cefadroxil and 0.95 % for ceftriaxone were obtained. Recoveries of cefadroxil tablets and ceftriaxone injection were in the range of 100.66 ± 0.98 and 99.38 ± 0.84 %, respectively. Conclusion: Recovery studies gave satisfactory results indicating that none of the major additives/excipients interfered with the assay method. Therefore, the proposed method is simple, rapid, precise and convenient for the assay of cefadroxil and ceftriaxone in commercial preparations