Mohamed G. El-Bardicy

Flow Injection Analysis of Pharmaceutical Compounds VII. Determination of Some Anthelmintic and Antiprotozoal Compounds

Abstract A simple continuous flow injection analysis (FIA) with spectrophotometric detection of some anthelmintic and ant iprotozoal drugs is presented. These drugs are; oxamniquine (OX), thiabendazole (TBZ), mebendazole (MBZ), flubendazole (FBZ), diloxanide furoate (DF), metronidazole (MTZ) and tinidazole (TNZ).

Simultaneous determination of domperidone maleate and cinnarizine in a binary mixture using derivative ratio spectrophotometry and classical least squares calibration

This work is concerned with the simultaneous determination of domperidone maleate (DOM) and cinnarizine (CINN) in a binary mixture form without previous separation by two different methods. The first method is the application of derivative ratio spectrophotometry where the linearity range was 2.5-30 micro g/ml, 2.5-25 micro g/ml for DOM and CINN, respectively, and percentage recoveries were 100.26+/-1.308 and 99.86+/-0.939 for DOM and CINN, respectively, in their laboratory prepared mixtures. The second method depends on the application of classical least squares (CLS) calibration model. Two training sets were constructed and the best model was used for the prediction of the concentrations of both drugs. The proposed procedures were successfully applied for the simultaneous determination of both drugs in laboratory prepared mixtures and in commercial tablet preparations. The validity of the proposed methods was assessed by applying the standard addition technique where the percentage recovery of the added standard was found to be 99.83+/-1.861 and 98.38+/-0.871 for DOM and CINN, respectively, using the derivative ratio method and 99.53+/-0.916 and 99.39+/-0.599 for DOM and CINN, respectively, using the CLS method. The proposed procedures are rapid, simple, require no preliminary separation steps and can, therefore, be used routine analysis of both drugs in quality control laboratories.

Determination of metformin hydrochloride in tablets by nuclear magnetic resonance spectrometry

Abstract The 1H-n.m.r. signal of the drug (10–35 mg ml−1) in deuterium oxide, with maleic acid as internal reference standard, is used. The integral of the peak at 3.06 ppm with respect to 3-trimethylsilylpropionic acid is compared with that at 6.3 ppm for the internal standard. The method is quantitative and free from interference by tablet excipients.

Comparative study of 2-hydroxy propyl beta cyclodextrin and calixarene as ionophores in potentiometric ion-selective electrodes for neostigmine bromide

Three novel neostigmine bromide (NEO) selective electrodes were investigated with 2-nitrophenyl octyl ether as a plasticiser in a polymeric matrix of polyvinyl chloride (PVC). Sensor 1 was fabricated using tetrakis(4-chlorophenyl)borate (TpClPB) as an anionic exchanger without incorporation of an ionophore. Sensor 2 used 2-hydroxy propyl β-cyclodextrin as an ionophore while sensor 3 was constructed using 4-sulfocalix-8-arene as an ionophore. Linear responses of NEO within the concentration ranges of 10(-5) to 10(-2), 10(-6) to 10(-2) and 10(-7) to 10(-2) mol L(-1) were obtained using sensors 1, 2 and 3, respectively. Nernstian slopes of 51.6 ± 0.8, 52.9 ± 0.6 and 58.6 ± 0.4 mV/decade over the pH range of 4-9 were observed. The selectivity coefficients of the developed sensors indicated excellent selectivity for NEO. The utility of 2-hydroxy propyl β-cyclodextrin and 4-sulfocalix[8]arene as ionophores had a significant influence on increasing the membrane sensitivity and selectivity of sensors 2 and 3 compared to sensor 1. The proposed sensors displayed useful analytical characteristics for the determination of NEO in bulk powder, different pharmaceutical formulations, and biological fluids (plasma and cerebrospinal fluid (CSF)) and in the presence of its degradation product (3-hydroxyphenyltrimethyl ammonium bromide) and thus could be used for stability-indicating methods.

Spectrophotometric and spectrodensitometric methods for the determination of rivastigmine hydrogen tartrate in presence of its degradation product.

Three sensitive, selective and precise stability-indicating methods for the determination of the anti-Alzheimers drug, rivastigmine hydrogen tartrate (RIV) in the presence of its alkaline degradation product (major metabolite, NAP 226-90) and in pharmaceutical formulation were developed and validated. The first method is a second derivative (D(2)) spectrophotometric one, which allows the determination of RIV in the presence of its degradate at 262 nm (corresponding to zero crossing of the degradate) over a concentration range of 50-500 microg/ml with mean percentage recovery 100.18 +/- 0.628. The second method is the first derivative of the ratio spectra (DD(1)) by measuring the peak amplitude at 272 nm over the same concentration range as (D(2)) spectrophotometric method, with mean percentage recovery 99.97 +/- 0.641. The third method is a TLC-densitometric one, where RIV was separated from its degradate on silica gel plates using methanol:butanol:H(2)O:ammonia (5:4:1:0.01 v:v:v) as a developing system. This method depends on the quantitative densitometric evaluation of thin layer chromatogram of RIV at 263 nm over a concentration range of 20-160 microg/spot, with mean percentage recovery 100.19 +/- 1.344. The selectivity of the proposed methods was tested using laboratory-prepared mixtures. The proposed methods have been successfully applied to the analysis of RIV in pharmaceutical dosage forms without interference from other dosage form additives and the results were statistically compared with reference method.

Stability-indicating spectrophotometric and spectrodensitometric methods for the determination of diacerein in the presence of its degradation product.

Three sensitive, selective, and precise stability-indicating methods for the determination of the novel osteoarthritis drug, diacerein (DIA) in the presence of its alkaline degradation product (active metabolite, rhein) and in pharmaceutical formulation were developed and validated. The first method is a first derivative (D(1) ) spectrophotometric one, which allows the determination of DIA in the presence of its degradate at 322 nm (corresponding to zero crossing of the degradate) over a concentration range of 4-40 µg/mL with mean percentage recovery 100.21 ± 0.833. The second method is the first derivative of the ratio spectra (DD(1) ) by measuring the peak amplitude at 352 nm over the same concentration range as (D(1) ) spectrophotometric method, with mean percentage recovery 100.09 ± 0.912. The third method is a TLC-densitometric one, where DIA was separated from its degradate on silica gel plates using ethyl acetate:methanol:chloroform (8:1.5:0.5 v:v:v) as a developing system. This method depends on quantitative densitometric evaluation of thin layer chromatogram of DIA at 340 nm over a concentration range of 1-10 µg/spot, with mean percentage recovery 100.24 ± 1.412. The selectivity of the proposed methods was tested using laboratory-prepared mixtures. The proposed methods have been successfully applied to the analysis of DIA in pharmaceutical dosage forms without interference from other dosage form additives and the results were statistically compared with reference method.

Bromometric determination of carbimazole

Direct bromometric titration of carbimazole using N-bromosuccinimide (NBS) in the presence of methyl red as indicator and three indirect titrations using NBS, potassium bromate and dibromohydantoin (DBH) are developed. The direct procedure can be adopted for quantities of carbimazole ranging from 2-12 mg with mean accuracies of 100.2 +/- 0.5. The indirect procedures can be used for quantities of the drug ranging from 1-6 mg using NBS and DBH and 2-16 mg using potassium bromate with mean accuracies of 100.11 +/- 0.3, 100.49 +/- 0.31 and 100.26 +/- 0.51 respectively. The proposed procedures have been successfully applied for the analysis of the drug in tablet form and their validity has been checked using the standard addition technique. The reaction products were separated by TLC methods and their structure was elucidated using IR and NMR spectroscopy. The stoichiometry and the possible pathways of the reaction were postulated and presented.

Stability-indicating methods for the determination of famciclovir in the presence of its alkaline-induced degradation product.

Five sensitive, selective and precise stability-indicating methods are presented for the determination of famciclovir (FCV) in the presence of its alkaline-induced degradation product. Method A utilizes the first derivative spectrophotometry at 321 nm. Method B depends on using the first derivative of the ratio spectrophotometry (DD(1)) by measurement of the amplitude at 256 nm. Method C is based on the reaction of FCV with hydroxylamine to form hydroxamic acid, causing the hydroxamic acid to react with triferric ion to form ferric hydroxamate that is measured at 503 nm. Method D is based on the separation of FCV from its degradation product followed by densitometric measurement of the bands at 304 nm. The separation was carried out on silica gel 60 F(254), using chloroform: methanol (70:30, v/v) as a mobile phase. Method E is based on a high performance liquid chromatographic (HPLC) separation of FCV from its degradation product using an ODS column with a mobile phase consisting of methanol-50 mM dipotassium hydrogen phosphate (25:75, v/v, pH 3.0)with UV detection at 304 nm. Regression analysis showed good correlation in the concentration ranges 16-72 microg/ml, 40-240 microg/ml, 40-240 microg/ml, 0.75-5.25 microg/band and 20-240 microg/ml with percentage recoveries of 99.65 +/- 0.85, 100.27 +/- 0.91, 99.72 +/- 0.84, 100.65 +/- 1.52 and 99.88 +/- 0.50 for methods A, B, C, D and E, respectively. These methods are suitable as stability-indicating methods for the determination of FCV in the presence of its degradation product either in bulk powder or in pharmaceutical formulation. Statistical analysis of the results has been carried out revealing high accuracy and good precision.

Determination of Carbimazole and Methimazole by First and Third Derivative Spectrophotometry

Abstract A rapid method for simultaneous determination of both carbimazole and methimazole by third derivative spectrophotometry is presented. First derivative spectrophotometry is also applied for selective determination of carbimazole in the presence of methimazole. By measuring the absolute values of the first (for carbimazole) and third derivative curves for the mixture, the concentration of each component can be calculated directly without interference from the other. The method was proved using prepared mixtures of the two drugs. The mean accuracies for the determination of carbimazole by first and third derivative spectrophotometry were found to be 100.02 ± 0.29, 100.07 ± 0.17, respectively and 99.97 ± 0.09 for methimazole by third derivative spectrophotometry. The proposed procedures were successfully applied for the analysis of carbimazole in tablet form and its validity was further checked using the standard addition technique.

STABILITY INDICATING METHOD FOR THE DETERMINATION OF NIZATIDINE USING 3-METHYL-2-BENZOTHIAZOLINONE HYDRAZONE

A sensitive stability indicating method for the determination of nizatidine in the presence of its degradation products is developed. The proposed method is based on measuring the peak heights of the first derivative spectra at 680 nm of the blue reaction product developed from the reaction of nizatidine with 3-methyl-2-benzothiazolinone hydrazone (MBTH) in the presence of ferric chloride. The concentration of MBTH, and type of oxidising agent and its concentration were studied over time. The suggested procedure is simple, rapid and readily adaptable for the determination of pure nizatidine in bulk powder. Laboratory prepared mixtures and pharmaceutical preparations in the range of 1.6–8 μg · ml−1 of reaction mixture can be analysed. The results obtained were compared statistically with those obtained by applying the official USP XXIII (1995) method. Furthermore, the validity of the results was assessed by applying the standard addition technique.