Mokhtar M. Mabrouk

Simultaneous determination of loratadine and pseudoephedrine sulfate in pharmaceutical formulation by RP-LC and derivative spectrophotometry ☆

Highly sensitive, simple and accurate reversed phase liquid chromatographic and first derivative spectrophotometric methods for determination of antihistaminic drug loratadine [I] and nasal decongestant drug pseudoephedrine sulfate [II] are described. The HPLC method involves separation of [I] and [II] on micro-BondaPak C18 column using mixture of (methanol:H(2)O:phosphoric acid:ammonium dihydrogen phosphate) (220:300:2:3 g) (V/V/V/W), 60 and 40% acetonitrile as mobile phase flowing at 2 ml/min with ultraviolet detection at 247 nm. The calibration graphs are linear from 5 to 100 microg/ml for [I] and from 120 to 1200 microg/ml for [II] the detection limits are 0.5 microg/ml for [I] and 60 microg/ml for [II]. The spectrophotometric method is based on recording the first derivative spectra for [I] and [II] at 307, 266 nm, respectively, of their solutions in 0.1 M hydrochloric acid using the acid as blank. The calibration graphs are linear in the range of 5-25 microg/ml for [I] and 240-720 microg/ml for [II]; the limits of detection are 0.16 microg/ml for [I] and 10 microg/ml for [II]. The mean percentage recoveries obtained for different synthetic mixtures by using this method are 97.6% with coefficient of variation 1.79 for [I] and 101.6% with coefficient of variation 1.95 for [II]. The two methods have been applied successfully for the determination of [I] in its combination with [II] Clarinase tablets and [I] alone in different pharmaceutical dosage forms.

Polarographic behaviour of loratadine and its direct determination in pharmaceutical formulation and human plasma by cathodic adsorptive stripping voltammetry.

The polarographic behaviour of the antihistaminic drug loratadine has been investigated in B.R. buffer solution of different pH values. Contradictory to that mentioned before in a previously published work, loratadine is electro-active at the mercury electrode. In B.R. buffer solution of pH values > or =6 it is reduced via a single 2-electrons irreversible wave corresponding to saturation of carbon-nitrogen double bond of the pyridine ring. The electrode reaction pathway was proposed and discussed. A sensitive differential pulse stripping voltammetric method based on controlled adsorptive accumulation of loratadine on a hanging mercury drop electrode has been developed for its direct determination at nanomolar concentrations without nitration of the drug. The optimized conditions for the direct cathodic adsorptive stripping voltammetric determination of the drug are: 0.1 M sodium hydroxide solution as a supporting electrolyte, accumulation potential, -1.2 V; accumulation time, 30 s; scan rate, 2-5 mV x s(-1) and pulse amplitude 100 mV. The proposed procedure was applied for the assay of loratadine in pharmaceutical formulation and human plasma. The average recoveries were 99.32-99.44 and 100.33-102.99% with the RSD 0.27-0.42 and 0.39-0.90% in pharmaceutical formulation and human plasma, respectively. The limits of detection of 1.60x10(-7) and 1.25x10(-7) M loratadine were found in pharmaceutical formulation and human plasma, respectively.

Direct determination of praziquantel in pharmaceutical formulations and human plasma by cathodic adsorptive stripping differential-pulse voltammetry

The polarographic and cyclic voltammetric behaviour of praziquantel was studied in B.R. buffers of different pH values. Contradictory to that mentioned in a previously published work, praziquantel is an electro-active compound. Its polarogram exhibited a single 2-electron irreversible reduction wave in B.R. buffer of pH 5, the wave height decreased on the increase of pH till it disappeared in solution of pH >7. This wave was attributed to the reduction of the Cz.dbnd6;O double bond. The quantitative trace determination of bulk praziquantel was studied at a hanging mercury drop electrode by cathodic adsorptive stripping differential-pulse voltammetry. A fully validated sensitive procedure based on controlled adsorptive accumulation of the drug onto a HMDE was developed for its direct determination without derivatization. Accumulation of praziquantel was found to be optimized in 0.1 M Na(2)SO(4) solution as supporting electrolyte under the following conditions: accumulation potential, -1.2 V (vs. Ag/AgCl/KCl(s)); accumulation time, 30 s; scan rate, 10 mV/s and pulse height 100 mV. The proposed procedure was applied successfully for determination of praziquantel in its pharmaceutical formulations and human plasma. The mean recoveries of the drug were 98.85-99.42% and 99.12-100.47% with RSD of 0.49-0.95% and 0.45-0.52% in pharmaceutical formulations and human plasma, respectively. Limits of detection and quantitation of 1.14x10(-9) and 3.80x10(-9) M praziquantel, respectively, were achieved.

Development and application of a novel, dual-mode gradient, stability-indicating HPLC-DAD method for the simultaneous determination and purity assessment of mebeverine hydrochloride, diloxanide furoate and their corresponding major degradation products in combination with some gastrointestinal drugs in the form of oral doses

A simple, precise, rapid, stability-indicating reversed phase high performance liquid chromatographic method with photodiode array detection was developed and validated for the determination of mebeverine hydrochloride in combination with sulpiride or with diloxanide furoate and metronidazole in the presence of their corresponding degradation products. Optimum separation was achieved in less than 10 min using an X-Bridge C18 column (150 mm × 4.6 mm i.d., 3.5 μm particle size); elution was accomplished via the application of a dual-mode solvent and flow rate gradient system. This elution system enables the separation of nine components within a cycle time of 15 min and with a resolution greater than 2.5. Detection was conducted at 230 nm, and purity assessment was performed using a photodiode array detector. The method has been validated with respect to specificity, linearity, accuracy, precision, limit of quantitation, limit of detection, robustness and ruggedness. The validation criteria were met in all cases. The developed HPLC method was successfully applied to commercial tablets. It was shown that this method is very sensitive to the determination of the degradation products, downward to 0.1 w/w% levels, which is far below the limits for testing these degradation products within their corresponding intact drugs.

Development and Validation of Chemometric-Assisted Spectrophotometric Methods for Simultaneous Determination of Phenylephrine Hydrochloride and Ketorolac Tromethamine in Binary Combinations.

The present work describes new spectrophotometric methods for the simultaneous determination of phenylephrine hydrochloride and ketorolac tromethamine in their synthetic mixtures. The applied chemometric techniques are multivariate methods including classical least squares, principal component regression, and partial least squares. In these techniques, the concentration data matrix was prepared by using the synthetic mixtures containing these drugs dissolved in distilled water. The absorbance data matrix corresponding to the concentration data was obtained by measuring the absorbances at 16 wavelengths in the range 244-274 nm at 2 nm intervals in the zero-order spectra. The spectrophotometric procedures do not require any separation steps. The accuracy, precision, and linearity ranges of the methods have been determined, and analyzing synthetic mixtures containing the studied drugs has validated them. The developed methods were successfully applied to the synthetic mixtures and the results were compared to those obtained by a reported HPLC method.

Fluorogenic derivatization of aryl halides based on the formation of biphenyl by Suzuki coupling reaction with phenylboronic acid

The fluorogenic derivatization method for aryl halide was developed for the first time. This method was based on the formation of fluorescent biphenyl structure by Suzuki coupling reaction between aryl halides and non-fluorescent phenylboronic acid (PBA). We measured the fluorescence spectra of the products obtained by the reaction of p-substituted aryl bromides (i.e., 4-bromobenzonitrile, 4-bromoanisole, 4-bromobenzoic acid ethyl ester and 4-bromotoluene) with PBA in the presence of palladium (II) acetate as a catalyst. The significant fluorescence at excitation maximum wavelength of 275-290 nm and emission maximum wavelength of 315-350 nm was detected in all the tested aryl bromides. This result demonstrated that non-fluorescent aryl bromides could be converted to the fluorescent biphenyl derivatives by the coupling reaction with non-fluorescent PBA. We tried to determine these aryl bromides by HPLC-fluorescence detection with pre-column derivatization. The aryl bromide derivatives were detected on the chromatogram within 30 min without any interfering peak derived from the reagent blank. The detection limits (S/N=3) for aryl bromides were 13-157 fmol/injection.

Effect of fenofibrate on indirect neonatal hyperbilirubinemia

Background: Neonatal jaundice is a cause for anxiety in parents as well as physicians due to its complications and prolonged hospital stay with increased cost. With early discharge practice, neonatal hyperbilirubinemia has become an important cause for readmission. Aim: The aim of this study is to evaluate the efficacy of oral fenofibrate in the treatment of neonatal hyperbilirubinemia in full term (FT) neonates due to ABO or Rh incompatibility. Design: The type of the study is prospective case control study. Patients and Methods: This study was carried out on 60 FT newborns suffering from neonatal hyperbilirubinemia due to ABO or Rh incompatibility and exaggerated physiological jaundice divided into two groups. Group A (control group): This group included 30 FT neonates with neonatal hyperbilirubinemia 19 males and 11 females. Their duration of stay ranged from 4 to 7 days. All the neonates in this group received phototherapy only. Group B (fenofibrate group): This group included 30 FT neonates with neonatal hyperbilirubinemia 20 males and 10 females. Their postnatal age ranged from day 1 to day 6. Their duration of stay ranged from 4 to 7 days. All the neonates in this group received one single oral dose of fenofibrate suspension with a dose 10 mg/kg beside phototherapy. Results: In our study, there was a statistically significant difference between the two groups (fenofibrate group vs. control group) as regard the response of babies to decrease the level of total serum bilirubin (TSB) and the duration of stay on phototherapy in hospital lower in fenofibrate group. We found that babies in fenofibrate group showed lower values in successive TSB levels and lower duration of stay in comparison to the control group. We studied the highest level of TSB reached during treatment and found that mean TSB of fenofibrate group was 15.797 mg/dl while mean TSB of the control group was 16.593 mg/dl. In our study, we found that the mean duration of stay at the hospital of fenofibrate group was 4.366 days, while mean duration of stay at the hospital of the control group was 5.633 days (P = 0.0058*). Conclusion: The use of a single oral dose of fenofibrate (with a dose 10 mg/kg) with phototherapy accelerates bilirubin conjugation and excretion via induction of glucuronyl transferase activity hence reduces the duration of stay in hospital.

Stability-indicating HPLC–DAD methods for determination of two binary mixtures: Rabeprazole sodium–mosapride citrate and rabeprazole sodium–itopride hydrochloride

Two selective stability-indicating HPLC methods are described for determination of rabeprazole sodium (RZ)–mosapride citrate (MR) and RZ–itopride hydrochloride (IO) mixtures in the presence of their ICH-stress formed degradation products. Separations were achieved on X-Bridge C18 column using two mobile phases: the first for RZ–MR mixture consisted of acetonitrile: 0.025 M KH2PO4 solution: TEA (30:69:1 v/v; pH 7.0); the second for RZ–IO mixture was at ratio of 25:74:1 (v/v; pH 9.25). The detection wavelength was 283 nm. The two methods were validated and validation acceptance criteria were met in all cases. Peak purity testing using contrast angle theory, relative absorbance and log A versus the wavelengths plots were presented. The % recoveries of the intact drugs were between 99.1% and 102.2% with RSD% values less than 1.6%. Application of the proposed HPLC methods indicated that the methods could be adopted to follow the stability of their formulations.

Simultaneous determination of amlodipine and metoprolol in their combined dosage form using a synchronous fluorescence spectrofluorimetric method

Highly sensitive, rapid, accurate and precise synchronous fluorescence spectrofluorimetric method has been developed for simultaneous analysis of a mixture of amlodipine (AMD) and metoprolol (MET). The method relies on measuring the relative synchronous fluorescence intensity of both drugs at Δλ of 90 nm in acetate buffer solution at pH 5. The experimental parameters influencing the developed method were investigated and optimized. The method was linear over the ranges 0.2-2 μg/ml and 0.5-10 μg/ml for AMD and MET, respectively. The limits of detection were 50 ng/ml for AMD and 130 ng/ml for MET while the limits of quantitation were 150 ng/ml for AMD and 390 ng/ml for MET. The developed method was applied successfully for the determination of the two drugs in their co-formulated tablet. The mean percent recoveries were found to be 100.51 and 99.57 for AMD and MET, respectively.

Three Spectrophotometric Methods for Determination of Alogliptin Benzoate and Pioglitazone HCl in Combined Tablet Dosage Form

Abstract Three simple, accurate and precise spectrophotometric methods have been developed and validated for simultaneous determination of alogliptin benzoate and pioglitazone HCl in bulk and in tablet dosage form. Method I was area under curve method and it involved measurement of area at selected wavelength range; the selected wavelength range was 275-285 nm for ALG and 263-273 nm for PIO. Method II involved the use of first derivative of ratio spectra (1DD) using PIO (10 μg/mL) as a divisor for ALG determination, then peak amplitude at 300 nm was directly proportional to ALG concentration; and ALG 5 μg/mL as a divisor for PIO determination, then peak amplitude at 277 nm was directly proportional to PIO concentration. Method III was ratio difference method and it involved measurement of difference in amplitudes (ΔP) in the ratio spectra; ΔP292-238 was directly proportional to ALG concentration and ΔP260-239 was directly proportional to PIO concentration. The three proposed methods were linear over the range 5-30 μg/mL for ALG and 5-50 μg/mL for PIO. The methods were validated according to ICH guidelines. Statistical comparison of the proposed methods with the reported HPLC method using F and t tests showed no significant difference regarding both accuracy and precision.