Stability-indicating methods for the determination of mosapride citrate in the presence of its degradation products according to ICH guidelines.

In the present work, different spectrophotometric methods and one spectrofluorimetric method have been developed and validated for the determination of mosapride citrate in the presence of its acid-induced degradation products. The drug was subjected to stress stability study including acid, alkali, oxidative, photolytic, and thermal stress degradation. The developed spectrophotometric methods included the use of first order derivative ((1)D), derivative of ratio spectra ((1)DD), mean centring of ratio spectra (MC) and H-point standard additions (HPSAM) spectrophotometric methods. For (1)D method, the peaks amplitudes at 282.8 and 319.6 nm were measured, while for (1)DD method those at 308 nm and 323 nm were measured. Mean centring of ratio spectra method used the values at 317 nm for calibration, while for HPSAM the absorbance at 273 and 288.6 nm were used. These methods were successfully applied for determination of mosapride in the concentration range of 5-70 µg.ml(-1). The spectrofluorimetric method was based on measuring the native fluorescence of mosapride in 0.1 M NaOH using λ(excitation) 276 nm and λ(emission) 344 nm and 684 nm with linearity ranges of 50-3000 ng.ml(-1) and 50-9000 ng.ml(-1), respectively. All the developed methods were validated according to the International Conference on Harmonization (ICH) guidelines and were applied for bulk powder and dosage form. The results obtained were statistically compared to each other using one-way ANOVA testing.

Miniaturized membrane sensors for potentiometric determination of metoprolol tartrate and hydrochlorothiazide.

Four microsized graphite and platinum wire poly(vinyl chloride) matrix membrane electrodes responsive to some drugs affecting cardiovascular system, Metoprolol tartrate (MT) and Hydrochlorothiazide (HZ) were developed, described and characterized. These sensors were constructed by using (2-Hydroxypropyl)-ß-cyclodextrin (2HP ß-CD) as an ionophore which has a significant influence on increasing both membrane sensitivity and selectivity. The four sensors were fabricated in a polymeric matrix of carboxylated polyvinyl chloride (PVC-COOH) and dioctylphthalate (DOP) as a plasticizer, based on the interaction between the drugs and the dissociated COOH groups in the PVC-COOH. Fast and stable Nernstian responses of 1.0 × 10-6-1.0 × 10-2 M for MT (sensors 1 and 2) and of 1.0 × 10-7-1.0 × 10-3 M for HZ (sensors 3 and 4) over pH range 3.0-9.0 and 3.0-7.0 for the MT and HZ sensors respectively were obtained. Nernstian slopes of 56.2, 54.6, 19.0 and 20.8 mV/decade for electrodes 1-4 respectively were observed. The proposed method displayed useful analytical characteristics for the determination of MT and HZ in their pure powder forms with average recoveries of 99.11 ± 0.357, 99.21 ± 0.389, 100.08 ± 0.459 and 100.28 ± 0.438% for sensors 1-4 respectively. The lower limit of detection (LOD) were 5.5 × 10-6, 4.5 × 10-6, 4.8 × 10-8 and 5.0 × 10-8 M for sensors 1-4 respectively indicated high sensitivity. The four sensors displayed a good stability over a period of 6 weeks. The selectivity coefficients of the developed sensors indicated excellent selectivity. Results obtained by the four electrodes revealed the performance characteristics of these electrodes which evaluated according to IUPAC recommendations. The method was successively applied for the determination of MT and HZ in presence of each other, in presence of Salamide (SA), the main degradation product of HZ, in their pharmaceutical formulations and in human plasma samples. Statistical comparison between the results obtained by this method and those obtained by the official methods of the drugs was done and no significant difference was found.

Simultaneous determination of metformin hydrochloride and pioglitazone hydrochloride in binary mixture and in their ternary mixture with pioglitazone acid degradate using spectrophotometric and chemometric methods.

In this work two well known oral hypoglycemic drugs that are administered in combination for patients with type-II diabetes were simultaneously determined. Several spectrophotometric methods were developed and validated for the determination of metformin hydrochloride (MET), pioglitazone hydrochloride (PIO) and pioglitazone acid degradate (PIO Deg). Derivative, ratio derivative, isosbestic and chemometric-assisted spectrophotometric methods were developed. The first derivative (D(1)) method was used for the determination of MET in the range of 5-30 microg x mL(-1) and PIO in the range of 10-90 microg x mL(-1) by measuring the peak amplitude at 247 nm and 280 nm, respectively. The concentration of PIO was calculated directly at 268 nm. The first derivative of ratio spectra (DD(1)) method used the peak amplitudes at 238 nm and 248.6 nm for the determination of MET in the range of 5-30 microg x mL(-1). In the isosbestic point method (ISO), the total mixture concentration was calculated by measuring the absorbance at 254.6 nm. Classical least squares (CLS), principal component regression (PCR) and partial least squares (PLS-2) were used for the quantitative determination of MET, PIO and PIO Deg. The methods developed have the advantage of simultaneous determination of the cited components without any pre-treatment. Resolution and quantitative determination of PIO degradate with a minimum concentration of 3 microg x mL(-1) in drug samples was done. The proposed methods were successfully used to determine each drug and the acid degradate in a laboratory-prepared mixture and pharmaceutical preparations. The results were statistically compared using one-way analysis of variance (ANOVA). The methods developed were satisfactorily applied to the analysis of the two drugs in pharmaceutical formulations.

Use of bioassay and microplate assay to detect and measure insecticide resistance in field populations of Culex pipiens from filariasis endemic areas of Egypt.

Insecticide and resistance bioassays and microplate assays were performed on Culex pipiens mosquitoes to determine the level and mechanisms of resistance. Culex pipiens larvae were collected from three filariasis-endemic areas of Egypt and reared to adults for subsequent production and testing of F1 generation larvae and adults. Bioassays were performed using World Health Organization (WHO) methods with the diagnostic doses of 6 organophosphate insecticides for larvae and 1 organochlorine (OC), 4 pyrethroid, 2 organophosphate, and 2 carbamate insecticides for adults. Microplate assays were performed to measure levels of beta esterase, acetylcholinesterase, insensitive acetylcholinesterase, oxidases, and glutathione-S-transferase enzymes. Larval bioassay results showed clear indications of resistance to organophosphate insecticides. Adult bioassays also showed widespread, significant resistance to many insecticides from all four classes, including the OC, DDT. The Qalubiya larval population was susceptible only to malathion, whereas Sharkiya larvae were susceptible to malathion, temephos, and chlorpyrifos. On the other hand, larval specimens from Assiut were resistant to all insecticides tested. Larval bioassay results were supported by those of microplate assays in showing elevated levels of glutathione S-transferase in populations from all three areas. In general, microplate results confirmed patterns of resistance observed using bioassays, and mechanisms of resistance were evident for all three areas sampled. Mechanisms of resistance are discussed in relation to microplate and bioassay results for the areas sampled and pesticides used.

Dipterous flies species and their densities in fourteen Egyptian Governorates.

The present study focused on dipterous flies, distribution and densities in 14 Egyptian Governorates. The abundance and distribution of flies was carried out in three phases. The first was in 1999 in 5 governorates, Qalyobia, Menoufia, Fayium, Behiera & Assuit included species of the families: Calliphoridae, Chloropidae, Drosophilidae, Milichiidae, Muscidae, Otitidae, Piophilidae, Sarcophagidae, Sepsidae, Sphaeroceridae and Syrphidae. The second was in 2000 in another five Governorates, Kafr-ElSheikh, Giza, Menia, Aswan and Sharkia included sp. of the families: Calliphoridae, Chloropidae, Drosophilidae, Milichiidae, Muscidae, Otitidae, Piophilidae, Sarcophagidae, Sepsidae, Sphaeroceridae and Syrphidae. The third phase was in 2001 in 4 Governorates: Kena, El-Wady El-Gedied, Da-kahlia and South Sinai included species of the families: Calliphoridae, Chloropidae, Drosophilidae, Milichiidae, Muscidae, Otitidae, Phoridae, Piophilidae, Sarcophagidae, Sepsidae, Sphaeroceridae and Syrphidae. Musca domestica was the most abundant sp. found throughout the work. The results are a step in drawing an update map for insect-vectors to help in the national control programs.

Mosquito species and their densities in some Egyptian governorates.

The present work studied the mosquito's identification, distribution and densities in fourteen Egyptian Governorates. The abundance and distribution of mosquito species monitored by three phases. The first was carried out in 1999 in five governorates, Qalyobia, Menoufia, Behaira, Fayium and Assuit. The second was in the year 2000 in Kafr El Sheikh, Giza, Sharkia, Menia and Aswan. The third was in the year 2001 in Kena, El Wady El Gadeed, Dakahlia and South Sinai. Culex species were the commonest mainly C. pipiens, C. antennatus and C. univittatus. C. thelerei was found only in El Kharga Oasis. Culiseta sp. was found in Qalyobia, Menofia, Behaira, Fayium, El Wady El Gadeed, Dakahlia and South Sinai and as larvae in Kafr El Sheikh, Giza, and Menia. Aedes detritus was found in Assiut, Fayium, Giza, Aswan, El Wady El Gadeed and South Sinai. Ae. caspius was found in Assiut and Aswan and as larvae in Kena and El Wady El Gadeed. Anopheles pharoensis was found in Behaira and Fayium, while A. algeriensis in Aswan. A. multicolor and A. sergentii were found in Fayium, Aswan and El Wady El Gadeed; but in Kena A. sergentii was found as larvae and A. multicolor as adults.

Field studies on the susceptibility of housefly to certain insecticides in nine Egyptian governorates.

Standard WHO test methods were used to determine the susceptibility of field population of housefly to four organophosphorous and two pyrethroid insecticides. Field population flies collected from nine governorates, Giza, Faiyoum, Suez, Behaira, Menoufia, Sharkia, Kafr El-Sheikh, Assiut and Aswan. The results indicated that, all tested insecticides were very effective on flies collected, from Sharkia, Kafr El-Sheikh and Aswan, but there was an evidence of increased vigor tolerance among those collected from Kafr El-Sheikh for bioresmethrin and tolerance for diazinon in Aswan. In Assiut, flies exhibited high sensitivity to diazinon, deltamethrin and bromophos while malathion was the least effective adulticide. Resistance to malathion, diazinon, fenthion and bioresmethrin was noticed in varying degrees at all governorates. The highest average resistance ratio was recorded for malathion in Behaira (55.3 folds) and in Suez (26 folds). Resistance was also more pronounced in Menoulia for diazinon (23.3 folds). As for bioresmethrin an apparent increase in the resistance ratio was detected in Suez (25 folds). In Giza. houseflies were resistant to fenthion (14.5 folds). Regarding the difference between the six insecticides used, deltamethrin was the most potent insecticide in all governorates.

Spectrophotometric determination of clobetasol propionate, halobetasol propionate, quinagolide hydrochloride, through charge transfer complexation.

Two spectrophotometric procedures are described for the determination of clobetasol propionate(I), halobetasol propionate(II) (corticosteroids) and quinagolide hydrochloride(III) (prolactin inhibitor). For corticosteroid drugs, the procedures are based on the formation of phenyl hydrazones of the corticosteroids which are subsequently subjected to charge transfer complexation reaction with either 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) as pi-acceptor or with iodine as sigma-acceptor. Prolactin inhibitor was reacted directly with the previous reagents. The molar ratios of the reactants were established and the experimental conditions were studied giving maximum absorption at 588 and 290 nm with DDQ and iodine methods, respectively for the three drugs. The concentration ranges were 20-150,50-300, and 20-80 microg ml(-1) in DDQ method for (I), (II), and (III), respectively and 13-20,15-40, and 8-32 microg ml(-1) in iodine method for (I), (II) and (III), respectively.