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An open, randomized, two-way crossover study was carried out in 28 healthy volunteers at Gulf Pharmaceutical Industries (Julphar), as a joint venture with Saqr Hospital, Ras Al-Khaimah, UAE. The two commercial brands used were Sarf (Julphar, UAE) as test and Ciprobay (Bayer AG, Germany) as reference product. The drug was administered to each subject with 240 mL of water after an overnight fasting in two treatment days separated by a one-week washout period. After dosing, serial blood samples were collected for a period of 24 hr and serum was separated and analyzed for ciprofloxacin using a sensitive, reproducible, and accurate high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. Various pharmacokinetic parameters, including AUC0-t, AUC0-infinity, Cmax, Tmax, t1/2, and lambdaz, were determined from ciprofloxacin serum concentration-time profiles for both formulations and found to be in good agreement with reported values. The parameters AUC0-t, AUC0-infinity, and Cmax were tested for bioequivalence after log-transformation of data. No significant difference was found based on analysis of variance (ANOVA); the 90% confidence intervals (95.73-107.62%, 94.98-108.26%, 92.80-103.90% for AUC0-t, AUC0-infinity, Cmax, respectively) for the test/reference ratios of these parameters were within the bioequivalence acceptance range of 80-125%. Based on this data, it is concluded that both formulations are bioequivalent and are interchangeable in medical practice.

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Two methods are presented for the determination of cefuroxime and cefadroxil in human urine using first (1D) derivative spectrophotometry and high-performance liquid chromatography. Cefuroxime and cefadroxil were determined by measurement of their first-derivative amplitude in 0.1 N sodium hydroxide at 292.5 and 267.3 nm, respectively in the concentration range of 2-10 microg ml(-1) for each drug. The HPLC method depends upon using a LiChrospher 100 RP-18 (5 microm) column at ambient temperature for cefuroxime and 35 degrees C for cefadroxil with mobile phases consisting of water-acetonitrile-acetic acid (85:15:0.1 v/v) at a flow rate of 1.5 ml min(-1) for cefuroxime; and 0.02 M potassium dihydrogen phosphate-acetonitrile (95:5 v/v) containing 0.003% (w/v) hexanesulphonic acid sodium salt and adjusted to apparent pH 3 with phosphoric acid at a flow rate of 2 ml min(-1) for cefadroxil. Quantitation was achieved with UV detection at 275 and 260 nm for cefuroxime and cefadroxil, respectively, based on peak area with linear calibration curves at the concentration ranges of 2-10 microg ml(-1) for cefuroxime and 5-20 microg ml(-1) for cefadroxil. The proposed methods were applied to the determination of dissolution rate for tablets and capsules containing each drug. The urinary excretion patterns as the cumulative amounts excreted have been calculated for each drug using the proposed methods.

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Spectrophotometric, atomic absorption spectrometric and high performance liquid chromatographic (HPLC) procedures have been developed for the determination of betahistine hydrochloride and captopril. The three procedures are based on the reaction of the drugs with carbon disulphide in alkaline medium with the formation of the dithiocarbamate or the trithiocarbonate derivative of betahistine (BHT) and captopril (CAP), respectively, then subsequent chelation with divalent metals. The absorbance measurement of the formed chelates or of the metal moiety of chelates was used as the basis for the spectrophotometric and atomic absorption spectrometric determinations. The formed complexes have been used as pre-column derivatizing procedure for the HPLC determination of the two drugs. The different experimental conditions were optimized. The calibration graphs were linear over the applicable concentration ranges. The proposed procedures were applied successfully for the determination of the two investigated drugs in their tablets dosage form.

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A simple, sensitive and selective spectrofluorimetric procedure was developed for the determination of amoxycillin, cefadroxil and cefoperazone. The method is based on the reaction between these drugs and ethyl acetoacetate, in acidic medium, to give yellow fluorescent products with excitation wavelengths ranging from 401 to 467 nm and emission wavelengths ranging from 465 to 503 nm. The reaction conditions were studied and optimized. The reaction obeyed Beer's law over the range of 10.0-20.0, 1.5-1.0 and 50.0-100.0 microg ml(-1) for amoxycillin, cefadroxil and cefoperazone, respectively. Interference's from other antibiotics, drugs and dosage forms additives, in capsules and vials dosage forms, were investigated. The proposed method was applied to the analysis of pharmaceutical formulations (capsules and vials) containing the above antibiotics, either alone or in combination with other antibiotics or drugs. The validity of the method was tested by the recovery studies of standard addition which were found to be satisfactory. The results of the proposed method demonstrated that the method is equally accurate, precise and reproducible as the official methods (USP XXIII) and those published for the non-official binary mixtures.

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Three methods are described for the simultaneous determination of mebeverine hydrochloride (MB) and sulpiride (SU) in combined pharmaceutical tablets. The first method depends on first-derivative ultraviolet spectrophotometry, with zero-crossing measurement method. The first derivative amplitudes at 214.2 and 221.6 nm were selected for the assay of MB and SU, respectively. Calibration graphs follow Beer's law in the range of 10-30 and 2-8 microg/ml(-1), and the linearity was satisfactory (r = 0.9999), for MB and SU, respectively. The second method was based on the application of the thin layer chromatographic separation of both drugs followed by the densitometric measurements of their spot areas. After separation on silica gel GF254 plates, using ethanol: diethyl ether: triethylamine (70:30:1 v/v) as the mobile phase, the chromatographic zones corresponding to the spots of MB and SU were scanned at 262 and 240 nm, respectively. The calibration function was established in the ranges of 4-12 microg for MB and 2-8 microg for SU. The third method was an internal standard procedure based on high performance liquid chromatographic separation of the two drugs on a reversed-phase, Bondapak CN column. The detection was done at 243 nm using buclizine hydrochloride as internal standard. All chromatographic methods showed good linearity, precision and reproducibility. No spectral or chromatographic interference from the tablet excipients were found. The proposed methods were successfully applied to the assay of commercial tablets and content uniformity test. The procedures were rapid, simple and suitable for quality control application.

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Derivative spectrophotometric, colorimetric and high performance liquid chromatographic methods, for the determination of the antihistaminic cetirizine dihydrochloride in tablet form were described. Spectrophotometrically, cetirizine was determined by the measurement of its first (1D) and second (2D) derivative amplitudes at 239 (peak) and 243-233 nm (peak-to-trough), respectively. The aqueous solutions obeyed Beer's law in the concentration ranges of 1.2-10.0 and 0.8-10.0 micrograms ml-1 for 1D and 2D measurements, respectively. The colorimetric procedure was based on measuring the absorbency of the coloured chromogen resulted from the reaction between cetirizine sodium salt in polar solvent (DMF) and chloranil at 556 nm. The relation with concentrations was linear over 120-250 micrograms ml-1. Optimization of the reaction conditions was studied. At the same time, investigation of the complex formed was made with respect to its composition and the associated constant. A simple liquid chromatographic assay has been developed for the determination of cetirizine dihydrochloride in the presence of one of its synthesis precursor (hydroxyzine hydrochloride). A Bondapak-C18 column was used with a mobile phase consisting of acetonitrile/0.01 M ammonium dihydrogen phosphate (32:68, v/v) containing 0.1% w/v tetrabutyl ammonium hydrogen sulphate adjusted to pH 3 with phosphoric acid at a flow rate of 2 ml min-1. With salicylic acid as internal standard, quantitation was achieved with UV detection at 230 nm based on the peak height ratios. Beer's law was obeyed in a concentration range of 3-35 micrograms ml-1 and the regression line equation was derived with a correlation coefficient of 0.9999. The validity of the methods was further confirmed using the standard addition method. The proposed procedures were successfully applied to the determination of cetirizine in bulk and tablet form, with high percentage of recovery, good accuracy and precision.

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A simple spectrophotometric method for the determination of timonacic is presented. The procedure is based on the chelate formation with palladium(II) chloride in buffered medium. The optimum conditions for the complex formation were ascertained and the method was developed for the determination of timonacic in the concentration range of 28-48 micrograms ml-1. The emperical formula of the formed complex was determined, by applying different spectrophotometric methods, at optimum pH of 4.8 and an ionic strength of mu = 0.5. The stoichiometric ratio was found to be 2:1 (timonacic/palladium) as calculated by the mole ratio, continuous variations and Asmus methods. The continuous variations and Nash methods were applied for the determination of the conditional stability constant of the formed yellow-water soluble complex and was found to be 3.27 x 10(7). The proposed methods was found to be suitable for the determination of timonacic in bulk and in its pharmaceutical tablets.

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Derivative spectrophotometry and high-performance liquid chromatography (HPLC) were used to determine tenoxicam and one of its decomposition products (2-aminopyridine) simultaneously and in the presence of each other. The derivative procedure was based on the linear relationship between the tenoxicam concentration and the second derivative amplitudes at 390-348 nm (peak-to-trough) measurement. The 2-aminopyridine was determined through measuring the second derivative amplitude at 241 nm (zero-crossing for tenoxicam). For the HPLC procedure, a reversed-phase C8 column with a mobile phase composed of 0.02 M sodium acetate-methanol-acetonitrile (11:8:1) with 0.005 M heptane sulfonic acid sodium salt, as an ion pair, was used to separate both compounds with 2,4-dinitrochlorobenzene, as an internal standard, in reasonable time. The flow rate was 1.5 ml min-1 with a programmable ultraviolet (UV) detection at 300 and 375 nm. Both UV derivative spectrophotometric and HPLC approaches were followed for confirming the purity of tenoxicam in bulk and tablets dosage form.

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Accurate, precise first-derivative ultraviolet spectrophotometric, gas-liquid and high performance liquid chromatographic methods for the determination of nifedipine and mefruside in tablet dosage form were described. The first-derivative method depends on measurements of the derivative amplitudes by peak-to-base and zero-crossing techniques, at 390 and 282 nm, for the determination of nifedipine and mefruside, respectively. Calibration graphs were linear (r = 0.9999) ranging from 8-40 and 20-60 micrograms ml-1 for nifedipine and mefruside, respectively, in presence of one another. The gas-liquid chromatographic method (GLC) was based on using cross-linked methylsilicone gum capillary column with flame ionization detector for the determination of nifedipine and mefruside in the binary mixture. The high performance liquid chromatographic (HPLC) method was based on using a reverse-phase column with a mobile phase of methanol-water (55-45, pH = 4.5) with UV detection at 260 nm. The three methods showed good linearity, precision and reproducibility. The proposed methods were successfully applied to the determination of both drugs in pharmaceutical tablets.

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Three methods are described for the simultaneous determination of nifedipine and acebutolol hydrochloride in combined pharmaceutical tablets. The first method depends on first-derivative ultraviolet spectrophotometry, with peak-to-base and zero-crossing measurements methods. The first derivative amplitudes at 400 and 352 nm were selected for the assay of nifedipine and acebutolol hydrochloride, respectively. Calibration graphs follow Beer's law in the range of 4-12 and 44-132 micrograms ml-1 and the linearity was satisfactory (r = 0.999) for nifedipine and acebutolol hydrochloride, respectively. The second method was based on the separation of nifedipine from acebutolol hydrochloride, with an internal standard thymolphthalein, using capillary gas-liquid chromatography with a programmable temperature change. The third method was based on high performance liquid chromatographic separation of the two drugs on a reversed-phase, C18, column using a mobile phase of methanol-water (55:45, pH 4.5) with a programmable flow rate of 1 ml min-1 for 4 min which changed to 2 ml min-1 for the rest of the run. The detection was done at 260 nm using oxprenolol hydrochloride as an internal standard. Both chromatographic methods showed good linearity, precision and reproducibility. No spectral or chromatographic interference from the tablet excipients were found. The proposed methods were successfully applied to the assay of commercial tablets and a content uniformity test. The procedures were rapid, simple nondestructive and suitable for quality control application.

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Simple and selective spectrophotometric procedures for the determination of mequitazine in its pharmaceutical tablets are described. The method was based on the formation of complex between mequitazine and palladium in presence of methyl cellulose in buffered or unbuffered media. The two procedures provide a mean of following the oxidative decomposition of the investigated drug. The apparent molar absorptivities at 460 and 500 nm were 2810 and 2840 and with Sandell's sensitivity of 0.116 and 0.103 for the buffered and unbuffered solutions, respectively. At the same time, Beer's law was obeyed in a concentration range of 2.4-7.2 mg% and the regression line equations were derived with correlation coefficients of 0.9997 and 0.9999 for buffered and unbuffered reactions, respectively. The validity of the method was further confirmed using the standard addition method. The proposed procedures demonstrate high percentage of recovery with good accuracy and precision.

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Spectrophotometric and spectrofluorimetric methods for the determination of two broad-spectrum fluoroquinolone antibacterials (ciprofloxacin and norfloxacin), either in pure form or in tablets, are described. Both methods are based on the formation of a ternary complex between palladium(II), eosin and the fluoroquinolone in the presence of methyl cellulose, as surfactant. Spectrophotometrically, under the optimum conditions, the ternary complexes showed an absorption maximum at 545 nm, with apparent molar absorptivities of 3.4 x 10(4) and 2.7 x 10(4) 1 mol-1 cm-1 and Sandell's sensitivities of 1.01 x 10(-2) and 1.12 x 10(-2) micrograms cm-2 for ciprofloxacin and norfloxacin, respectively. The solution of the ternary complex obeyed Beer's law in the concentration range 3-10 micrograms ml-1 for both quinolones. The proposed method was applied to the determination of the two drugs in pharmaceutical tablets. A fluorescence quenching method for the determination of both quinolones by forming this ternary complex was also investigated for the purpose of enhancing the sensitivity of the determination. The results obtained by the application of both procedures and the USP XXIII methods were in good agreement and statistical comparison by means of Student's t-test and the variance ratio F-test showed no significant differences between the three methods.

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Two methods are described for the simultaneous determination of enalapril maleate and hydrochlorothiazide in combined pharmaceutical tablets. The first method depends on first-derivative ultraviolet spectrophotometry, with zero-crossing and peak-to-base measurement methods. The first-derivative amplitudes at 224 and 260 nm were selected for the assay of enalapril maleate and hydrochlorothiazide, respectively. The second method is based on high-performance liquid chromatography on a reversed-phase column using a mobile phase of acetonitrile-water (20:80, v/v) (pH 3.8) with programmable detection at 215 and 275 nm. Both methods showed good linearity, precision and reproducibility. The proposed methods were successfully applied to the determination of these drugs in laboratory-prepared mixtures and in commercial tablets.

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A simple, stability-indicating liquid chromatographic method has been developed for the assay of flunarizine dihydrochloride in the presence of its acid-induced degradation product. A Bondapak-C18 column was used with a mobile phase consisting of methanol-water (75:25, v/v) containing 0.5% w/v sodium chloride and 0.2% v/v triethanolamine adjusted to pH 6.6 with 30% hydrochloric acid at a flow rate 2 ml min-1. Quantitation was achieved with UV detection at 254 nm based on peak area or peak height ratios. The proposed method was successfully applied to the determination of the drug in laboratory-prepared mixtures in the presence of its degradation product and in capsules. Moreover, the method was utilized to investigate the kinetics of the degradation process at different temperatures and the apparent first-order rate constant, half-life and activation energy calculated.

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A spectrophotometric method is described for the assay of flunarizine dihydrochloride. The method is based on the molecular interaction between the drug and iodine, to form a charge-transfer complex in which the drug acts as n-donor and iodine as sigma-acceptor. The iodine was found to form charge-transfer complex in a 1:1 stoichiometry with absorption bands at 295 and 355 nm. The concentrations were linear over 8-13 micrograms ml-1 at both 295 and 355 nm, respectively. A complete, detailed investigation of the formed complex was made with respect to its composition, associated constant and free energy change. The method has been applied successfully to the analysis of commercially available flunarizine dihydrochloride capsules without interference from the capsules excipient. To validate the proposed method, its accuracy and precision, the results were statistically compared with a newly developed reversed-phase HPLC procedure using Student-t and F-ratio tests.

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Two rapid assay procedures based on high-performance liquid chromatography (HPLC) and derivative ultraviolet (UV) spectrophotometry have been developed for the simultaneous determination of amoxycillin and dicloxacillin in two-component capsule formulations. The HPLC determination was carried out on a reversed-phase C8 column with use of a mobile phase consisting of methanol-0.02 mol dm-3 ammonium acetate (pH 5) (50 + 50) at a flow rate of 1.0 cm3 min-1, with UV detection at 230 nm. The fourth-derivative spectrophotometric procedure depends on the measurement of the derivative amplitudes, in 0.1 mol dm-3 NaOH, at 308.5 and 275 nm for amoxycillin and dicloxacillin, respectively. For both procedures, the calibration graphs were linear in the ranges 20-200 and 20-140 micrograms cm-3 for the HPLC and UV derivative methods, respectively, with an almost zero intercept and a correlation coefficient of 0.999. Commercial capsules and laboratory-prepared mixtures containing both penicillins in different proportions were assayed by the developed procedures. The results were of comparable accuracy as indicated by a statistical analysis of the data, using both t- and F-tests.

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Procarbazine was shown to decrease spermatogenesis in male mice in a dose-dependent manner. Significant decreases (44% of controls) in spermatogenesis were observed when a dose of 400 mg/kg was administered 18 days prior to determination of sperm count. Procarbazine caused no significant acute spermatocidal activity in vivo. Procarbazine-associated decreases in spermatogenesis were thus used as an index of toxicity to developing spermatid cells. Procarbazine analogs were synthesized that had deuterium substituted for hydrogen at the benzylic position, N-isopropyl-alpha-(2-methylhydrazino)-p-[alpha, alpha-2H2]toluamide (d2-procarbazine), or at the methyl position, N-isopropyl-alpha-(2-[alpha, alpha, alpha-2H3]methylhydrazino)-p-toluamide (d3-procarbazine). Spermatogenesis decreases caused by d3-procarbazine were essentially the same as with procarbazine in mice (66% of controls at a dose of 200 mg/kg), but d2-procarbazine was nontoxic to developing sperm cells (99% of control at a dose of 200 mg/kg). The decrease in toxicity caused by deuterium substitution at the benzylic position, coupled with the absence of an effect with the methyl-labeled analog, indicate the requirement for regioselective oxidative metabolism of procarbazine at the benzylic position prior to the toxic event.

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