Sensitive derivatization methods for the determination of genotoxic impurities in drug substances using hyphenated techniques.

Six sensitive derivatization methods for the determination of genotoxic impurities in selected drug substances were developed using hyphenated techniques. Some of the raw materials, reagents and reaction intermediates of the selected drug substances were identified as genotoxic impurities through DEREK software for windows. The genotoxic impurities which are amenable for derivatization were selected as substrates. Derivatizing agents were selected based on the functional groups of the genotoxic impurities. The chemistry involved in the derivatization was explained with suitable mechanisms. An appropriate hyphenated technique viz. LC-MS and GC-MS was opted based on the sensitivity and aromaticity of the derivatized genotoxic impurities. All the methods were validated as per International Conference on Harmonization guidelines. Correlation coefficient values were found about 0.99. The obtained % R.S.D values from replicate injections in the range of 2.3-4.8 and % recoveries of the added impurities in the range of 83.7-101.7 ensured the precision and accuracy, respectively.

Development and validation of LC methods with visible detection using pre-column derivatization and mass detection for the assay of voglibose.

Two sensitive and selective liquid chromatographic methods were developed for the assay of voglibose (VB) and validated as per International Conference on Harmonization (ICH) guidelines. First method is based on the pre-column derivatization of VB followed by visible detection (LC-VD) and second method involves mass spectrometric detection (LC-MS). In LC-VD method, VB was derivatized with sodium metaperiodate and 3-methyl-2-benzothiazolinone hydrazone hydrochloride monohydrate (MBTH). The derivatized color product of VB (DCPVB) was run through Novapak C18 (300 x 3.9 mm, 4 microm) column using the mobile phase containing buffer (0.01 M mixture of sodium di hydrogen orthophosphate and disodium hydrogen orthophosphate, pH 6.0) and acetonitrile in 35:65 v/v ratio. The eluted DCPVB was monitored at 667 nm. The fixation of optimum conditions in LC-VD method is described. DCPVB structure was confirmed by mass spectral analysis. In LC-MS method, VB was passed through Venusil XBPPH (150 x 4.6 mm, 5 microm) column using a 95:5 v/v mixture of 0.01% formic acid and methanol as mobile phase. The assay concentrations of VB in pure form and in tablets for LC-VD and LC-MS methods are 25 and 5 ngml(-1), respectively.

Ru(III)-catalyzed oxidation of pyridoxine and albuterol in pharmaceuticals.

Ru(III) complexes with coordinated amide were synthesized and characterized by elemental, IR, mass, electronic, ESR spectral analysis, magnetic and conductance measurements and octahedral structures have been proposed. These complexes were used as catalysts for the oxidation of pyridoxine and albuterol in pharmaceuticals in presence of hydrogen peroxide. The role of co-oxidant and the effect of reaction time on the yields of oxidation products which were spectrophotometrically determined by condensing them with sulfanilic acid in acid medium were investigated. Structures of the oxidation products were established with the help of IR and NMR spectral analysis.

Catalytic reduction of pralidoxime in pharmaceuticals by macrocyclic Ni(II) compounds derived from orthophthalaldehyde.

Efficient catalytic method for the reduction of pralidoxime to its amine derivative by macrocyclic Ni(II) compounds has been developed. Ten macrocyclic Schiff base Ni(II) compounds were synthesized via non-template synthesis by treating the corresponding macrocycles with nickel chloride in 1:1 ratio. The resulting compounds were characterized by elemental, IR, (1)H NMR, (13)C NMR, mass, electronic spectra, conductance, magnetic, thermal studies and their structures have been proposed. These compounds were used as catalysts for the reduction of pralidoxime to its amino derivative. The reduced pralidoxime was also characterized by spectral analysis and catalytic cycle has been established. The reduced product was determined spectrophotometrically by treating with ninhydrin reagent and the percent yields were found to be in the range of 75.12-82.36%.

Synthesis, spectral studies and antibacterial activity of novel macrocyclic Co(II) compounds.

Ten novel macrocyclic Co(II) compounds have been synthesized by treating four N(4) and six N(2)O(2) donor macrocycles with cobalt chloride in methanol. These compounds were characterized by elemental, IR, (1)H, (13)C NMR, mass, electronic spectral analysis, molar conductance and magnetic susceptibility measurements. Thermal behavior of these compounds has been studied by the thermogravimetric analysis. An octahedral geometry has been proposed for all of these complexes. All the macrocycles and macrocyclic Co(II) compounds along with existing antibacterial drugs were screened for antibacterial activity against Gram +ve and Gram -ve bacteria. All these compounds were found to be more active when compared to streptomycin and ampicillin.

Determination of minocycline by oxidative coupling and diazocoupling reactions in pharmaceutical formulations.

Simple and sensitive spectrophotometric methods (M(1)-M(4)) by the application of oxidative coupling and diazocoupling reactions for the assay of minocycline (MC) in pure form and pharmaceutical formulations have been described. Methods M(1) and M(2) involve the oxidative coupling reactions of MC with 3-methyl-2-benzothiozolinone hydrazone (MBTH) (method M(1), lambda(max) 440 nm) or 4-aminophenazone (4-AP) (method M(2), lambda(max) 520 nm) in the presence of periodate. Methods M(3) and M(4) are based on the formation of diazocoupling products of MC with diazotised p-nitroaniline (DPNA) (method M(3), lambda(max) 420 nm) or diazotised sulfanilic acid (DSAC) (method M(4), lambda(max) 420 nm). Regression analysis of Beer's law plot showed good correlation in the concentration range of 8-48, 20-120, 4-20 and 8-40 microg ml(-1) for methods A, B, C and D, respectively. The molar absorptivities fell within the range of 2.23 x 10(3)-1.51 x 10(4) l mol(-1) cm(-1). The recoveries range from 99.02 to 100.61%.