Determination of dexamethasone and lenalidomide in plasma by SPE and UPLC-MS/MS for the purpose o... more Determination of dexamethasone and lenalidomide in plasma by SPE and UPLC-MS/MS for the purpose of TDM: application to pharmacokinetic studies.
This study describes, for the first, the spectrophotometric investigation for the condensation re... more This study describes, for the first, the spectrophotometric investigation for the condensation reaction between varenicline (VRC) and cyclohexa-3,5-diene-1,2-dione (CHDD). The reaction gave a violet-colored product exhibiting maximum absorption peak (λmax) at 540 nm. The variables affecting the reaction were carefully investigated and the optimum conditions were established. The stoichiometry of the reaction was determined, and the reaction pathway was postulated. This color-developing reaction was employed in the development of microwell plate assay for VRC. In this assay, the reaction was carried out in 96-microwell plate and the absorbance of the colored-product was measured by microwell plate absorbance reader. Under the optimized reaction conditions, Beer’s law correlating the absorbance with VRC concentration was obeyed in the range of 5 - 100 μg/mL with good correlation coefficient (0.9986). The limits of detection and quantification were 2.29 and 6.95 μg/mL, respectively. Th...
A novel method based on microemulsion electrokinetic chromatography (MEEKC) with reversed electro... more A novel method based on microemulsion electrokinetic chromatography (MEEKC) with reversed electrode polarity stacking mode (REPSM) was developed and validated for the simultaneous determination of dexamethasone sodium phosphate (DEX-SP) and the active drug dexamethasone (DEX) in rabbit plasma. The optimum separation was achieved when using a microemulsion background electrolyte consisting of 30 mM borate buffer (pH 9.2), 20 mM sodium dodecyl sulfate (SDS), 0.8 % ethyl acetate and 2% 1-butanol. Electrophoretic separation was carried out at 24ºC and at +23 KV. The stacking technique has been developed to pre-concentrate samples and to increase the amount of sample that can be loaded onto the capillary without degrading the separation, up to 160 sec. REPSM was applied using the following optimized program as follows: + 23 KV (0-0.6 min) then -23 KV (0.6-1.5 min) and finally +23 KV for the rest of the run. The analytes were base-line resolved within 12 min. Using hydrochlorothiazide (HC...
Clenbuterol enantiomers were directly separated and determined in plasma and pharmaceutical formu... more Clenbuterol enantiomers were directly separated and determined in plasma and pharmaceutical formulation by a selective HPLC method using cellulose-based polysaccharide chiral stationary phase (CSP) known as OJ-RH. Enantiomeric resolution was achieved with a mobile phase consists of acetonitrile: 0.3M sodium perchlorate (16 %: 84 %), (v/v), a flow rate of 0.9 ml/min and a UV detection set at 247 nm. The method validated for its linearity, accuracy, and precision and robustness. The standard calibration curves were linear over the range of 0.5-50 μg/ml for each enantiomer with detection limit of 0.1 μg/ml. There was no significant difference between inter- and intra-day studies for each enantiomer which confirmed the reproducibility of the assay method. The method is highly specific where the co-formulated compounds did not interfere. The stability of clenbuterol enantiomers under high temperature was studied. The results showed that the drug is stable for at least 7 days at 80oC. The...
This study describes the development and validation of a new 96-micorwell-based spectrophotometri... more This study describes the development and validation of a new 96-micorwell-based spectrophotometric assay with high-throughput for pharmaceutical quality control of lenalidomide (LND), the new drug for treatment of multiple myeloma. The reaction between LND and 1,2-naphthoquinone-4- sulphonate (NQS) as a chromogenic reagent was investigated. In alkaline medium (pH 9), a red-colored product exhibiting maximum absorption peak (λmax) at 462 nm was produced. The stoichiometry and kinetic of the reaction were investigated and the reaction mechanism was postulated. This color-developing reaction was employed, for the first time, in the development of the proposed assay. The reaction was carried out in 96-microwell plate and the absorbance of the colored-product was measured by microwell plate absorbance reader at 450 nm. The optimized reaction conditions were established; under which, Beer’s law correlating the absorbance with LND concentration was obeyed in the range of 3-100 μg/mL with a...
ABSTRACT Capillary electrophoresis with a diode array detector was employed for the determination... more ABSTRACT Capillary electrophoresis with a diode array detector was employed for the determination of luteolin and apigenin in plant extracts. The experimental factors affecting the elution of the analytes were carefully optimized. The final analysis was achieved utilizing a fused silica capillary (58 cm effective length, 75 µm ID) and a background electrolyte solution consisting of borax buffer (20 mM, pH 10.0) and methanol (90: 10, v/v) with a 23 kV driving voltage and detection at 210 nm. The method was fully validated as per the guidelines of the International Conference on Harmonization for Analytical Procedures. The relationship between peak area and concentration was linear between 3 and 800 µg/mL for both compounds with detection limits of 1.05 for luteolin and 0.53 µg/mL for apigenin. The method was employed for the determination of the analytes in extracts of thyme and parsley. Both compounds were resolved from interfering peaks that were present in the extracts. Recovery studies were performed by fortifying the extracts with standards and demonstrated good accuracy with recovery values between 97.29 and 104.88% for luteolin and 96.89 and 105.18% for apigenin. Thyme and parsley were shown to contain high concentrations of luteolin and apigenin.
Iranian journal of pharmaceutical research : IJPR, 2014
A simple and rapid stability indicating method based on capillary zone electrophoresis has been d... more A simple and rapid stability indicating method based on capillary zone electrophoresis has been developed and validated for the analysis of buserelin (BUS). The best separations were achieved by using a bare fused silica capillary (75 μm i.d.; 65.5 cm total, 57.0 cm effective length), phosphate buffer (pH = 3.00; 26.4 mM), at 35 °C. The sample was hydrodynamically injected at 50 mbar for 5 seconds; the applied voltage was 30 kV and detection was carried out by UV-absorbance at 200 nm. Method validation resulted in the following figures of merit : the method was linear in the concentration range between 0.781 and 500 μg/mL (linear regression coefficient 0.9996), accuracy was between 99.3% and 100.9%, intra assay precision was between 0.3% and 1.0% and intermediate precision was between 1.0% and 2.1%. Evaluation of the specificity of the method showed no interference between excipients or products of force degradation and BUS. Under the selected conditions, separation of BUS and its d...
A high-performance liquid chromatographic (HPLC) method has been developed for the separation and... more A high-performance liquid chromatographic (HPLC) method has been developed for the separation and determination of S- and R-enantiomers of betaxolol in tablets and ophthalmic preparations. Baseline resolution was achieved by using teicoplanin macrocyclic antibiotic chiral stationary phase (CSP) known as Chirobiotic T with fluorescence detection at excitation/emission wavelengths 275/305 nm. The polar ionic mobile phase (PIM) consists of methanol-glacial acetic acid-triethylamine, (100:0.020:0.025, v/v/v) has been used at a flow rate of 1.5 ml/min. All analytes with S-(-)-atenolol as internal standard were conducted at ambient temperature. The method is highly specific where another coformulated compounds did not interfere. The stability of betaxolol enantiomers under different degree of temperature also studied. The results showed that it is stable for at least 7 days at 70 degrees C. The method validated for its linearity, accuracy, precision and robustness. Experimental design was...
MEEKC electropherograms of (A) a standard mixture of (2.0 μg mL−1) HCT, (1), DEX-SP, (2), and DEX... more MEEKC electropherograms of (A) a standard mixture of (2.0 μg mL−1) HCT, (1), DEX-SP, (2), and DEX, (3) and (B) the treated rabbit plasma sample.
A novel method was developed for the simultaneous determination of guaifenesin (GUA) and ketorola... more A novel method was developed for the simultaneous determination of guaifenesin (GUA) and ketorolac tromethamine (KET) enantiomers in plasma samples. Since GUA probably increases the absorption of coadministered drugs (e.g., KET), it would be extremely important to monitor KET plasma levels for the purpose of dose adjustment with a subsequent decrease in the side effects. Enantiomeric resolution was achieved on a polysaccharide-based chiral stationary phase, amylose-2, as a chiral selector under the normal phase (NP) mode and using ornidazole (ORN) as internal standard. This innovative method has the advantage of the ease and reliability of sample preparation for plasma samples. Sample clean-up was based on simply using methanol for protein precipitation followed by direct extraction of drug residues using ethanol. Both GUA and KET enantiomers were separated using an isocratic mobile phase composed of hexane/isopropanol/trifluoroacetic acid, 85:15:0.05 v/v/v. Peak area ratios were linear over the range 0.05-20 µg/mL for the four enantiomers S (+) GUA, R (-) GUA, R (+) KET, and S (-) KET. The method was fully validated according to the International Conference on Harmonization (ICH) guidelines in terms of system suitability, specificity, accuracy, precision, robustness, and solution stability. Finally, this procedure was innovative to apply the rationale of developing a chiral high-performance liquid chromatography (HPLC) procedure for the simultaneous quantitative analysis of drug isomers in clinical samples.
A novel, fast, sensitive, and specific capillary electrophoresis (CE) technique coupled to a diod... more A novel, fast, sensitive, and specific capillary electrophoresis (CE) technique coupled to a diode array detector has been developed for the separation and simultaneous determination of carvedilol (CRV) and hydrochlorothiazide (HCT) in two combination formulations. The proposed method utilized a fused silica capillary (55 cm × 75 μm id) and the background electrolyte solution phosphate buffer (12.5 mM, pH 7.4)–methanol (95 + 5, v/v). The separation was achieved at 30 kV applied voltage and 24°C. Atorvastatin (80 μg/mL) was chosen as the internal standard. The described method was linear over the range of 1–200 and 0.2–150 μg/mL for CRV and HCT, respectively. Intraday and interday RSD (n = 6) was ≤1.4%. The LOD values of CRV and HCT were 0.26 and 0.07 μg/mL, respectively. The validated CE method was successfully applied to the analysis of two commercial tablet dosage forms. Forced degradation studies were performed on bulk samples of the two drugs using thermal, photolytic, hydrolyti...
Enantiomeric resolution of atenolol was achieved on the HPLC vancomycin macrocyclic antibiotic ch... more Enantiomeric resolution of atenolol was achieved on the HPLC vancomycin macrocyclic antibiotic chiral stationary phase Chirobiotic V. The polar ionic mobile phase consisted of methanol–glacial acetic acid–triethylamine (100 + 0.025 + 0.75, v/v/v) at a flow rate of 0.8 mL/min. Fluorescence detection at 275/305 nm for excitation and emission, respectively, was used. Plasma samples were purified using SPE on Oasis HLB cartridges. The calibration curves in plasma were linear over the range of 5–400 ng/mL (r = 0.999) for each enantiomer with an LOD of 1.0 ng/mL. The proposed method was validated in compliance with International Conference of Harmonization guidelines in terms of linearity, accuracy, precision, LOD, LOQ, and selectivity. The overall recoveries for S-(–)- and R-(+)-atenolol enantiomers from plasma were 95.0–99.5%; RSD ranged from 2.5 to 3.3%. The developed method was applied for the trace analysis of atenolol enantiomers in plasma and for the pharmacokinetic investigation o...
Determination of dexamethasone and lenalidomide in plasma by SPE and UPLC-MS/MS for the purpose o... more Determination of dexamethasone and lenalidomide in plasma by SPE and UPLC-MS/MS for the purpose of TDM: application to pharmacokinetic studies.
This study describes, for the first, the spectrophotometric investigation for the condensation re... more This study describes, for the first, the spectrophotometric investigation for the condensation reaction between varenicline (VRC) and cyclohexa-3,5-diene-1,2-dione (CHDD). The reaction gave a violet-colored product exhibiting maximum absorption peak (λmax) at 540 nm. The variables affecting the reaction were carefully investigated and the optimum conditions were established. The stoichiometry of the reaction was determined, and the reaction pathway was postulated. This color-developing reaction was employed in the development of microwell plate assay for VRC. In this assay, the reaction was carried out in 96-microwell plate and the absorbance of the colored-product was measured by microwell plate absorbance reader. Under the optimized reaction conditions, Beer’s law correlating the absorbance with VRC concentration was obeyed in the range of 5 - 100 μg/mL with good correlation coefficient (0.9986). The limits of detection and quantification were 2.29 and 6.95 μg/mL, respectively. Th...
A novel method based on microemulsion electrokinetic chromatography (MEEKC) with reversed electro... more A novel method based on microemulsion electrokinetic chromatography (MEEKC) with reversed electrode polarity stacking mode (REPSM) was developed and validated for the simultaneous determination of dexamethasone sodium phosphate (DEX-SP) and the active drug dexamethasone (DEX) in rabbit plasma. The optimum separation was achieved when using a microemulsion background electrolyte consisting of 30 mM borate buffer (pH 9.2), 20 mM sodium dodecyl sulfate (SDS), 0.8 % ethyl acetate and 2% 1-butanol. Electrophoretic separation was carried out at 24ºC and at +23 KV. The stacking technique has been developed to pre-concentrate samples and to increase the amount of sample that can be loaded onto the capillary without degrading the separation, up to 160 sec. REPSM was applied using the following optimized program as follows: + 23 KV (0-0.6 min) then -23 KV (0.6-1.5 min) and finally +23 KV for the rest of the run. The analytes were base-line resolved within 12 min. Using hydrochlorothiazide (HC...
Clenbuterol enantiomers were directly separated and determined in plasma and pharmaceutical formu... more Clenbuterol enantiomers were directly separated and determined in plasma and pharmaceutical formulation by a selective HPLC method using cellulose-based polysaccharide chiral stationary phase (CSP) known as OJ-RH. Enantiomeric resolution was achieved with a mobile phase consists of acetonitrile: 0.3M sodium perchlorate (16 %: 84 %), (v/v), a flow rate of 0.9 ml/min and a UV detection set at 247 nm. The method validated for its linearity, accuracy, and precision and robustness. The standard calibration curves were linear over the range of 0.5-50 μg/ml for each enantiomer with detection limit of 0.1 μg/ml. There was no significant difference between inter- and intra-day studies for each enantiomer which confirmed the reproducibility of the assay method. The method is highly specific where the co-formulated compounds did not interfere. The stability of clenbuterol enantiomers under high temperature was studied. The results showed that the drug is stable for at least 7 days at 80oC. The...
This study describes the development and validation of a new 96-micorwell-based spectrophotometri... more This study describes the development and validation of a new 96-micorwell-based spectrophotometric assay with high-throughput for pharmaceutical quality control of lenalidomide (LND), the new drug for treatment of multiple myeloma. The reaction between LND and 1,2-naphthoquinone-4- sulphonate (NQS) as a chromogenic reagent was investigated. In alkaline medium (pH 9), a red-colored product exhibiting maximum absorption peak (λmax) at 462 nm was produced. The stoichiometry and kinetic of the reaction were investigated and the reaction mechanism was postulated. This color-developing reaction was employed, for the first time, in the development of the proposed assay. The reaction was carried out in 96-microwell plate and the absorbance of the colored-product was measured by microwell plate absorbance reader at 450 nm. The optimized reaction conditions were established; under which, Beer’s law correlating the absorbance with LND concentration was obeyed in the range of 3-100 μg/mL with a...
ABSTRACT Capillary electrophoresis with a diode array detector was employed for the determination... more ABSTRACT Capillary electrophoresis with a diode array detector was employed for the determination of luteolin and apigenin in plant extracts. The experimental factors affecting the elution of the analytes were carefully optimized. The final analysis was achieved utilizing a fused silica capillary (58 cm effective length, 75 µm ID) and a background electrolyte solution consisting of borax buffer (20 mM, pH 10.0) and methanol (90: 10, v/v) with a 23 kV driving voltage and detection at 210 nm. The method was fully validated as per the guidelines of the International Conference on Harmonization for Analytical Procedures. The relationship between peak area and concentration was linear between 3 and 800 µg/mL for both compounds with detection limits of 1.05 for luteolin and 0.53 µg/mL for apigenin. The method was employed for the determination of the analytes in extracts of thyme and parsley. Both compounds were resolved from interfering peaks that were present in the extracts. Recovery studies were performed by fortifying the extracts with standards and demonstrated good accuracy with recovery values between 97.29 and 104.88% for luteolin and 96.89 and 105.18% for apigenin. Thyme and parsley were shown to contain high concentrations of luteolin and apigenin.
Iranian journal of pharmaceutical research : IJPR, 2014
A simple and rapid stability indicating method based on capillary zone electrophoresis has been d... more A simple and rapid stability indicating method based on capillary zone electrophoresis has been developed and validated for the analysis of buserelin (BUS). The best separations were achieved by using a bare fused silica capillary (75 μm i.d.; 65.5 cm total, 57.0 cm effective length), phosphate buffer (pH = 3.00; 26.4 mM), at 35 °C. The sample was hydrodynamically injected at 50 mbar for 5 seconds; the applied voltage was 30 kV and detection was carried out by UV-absorbance at 200 nm. Method validation resulted in the following figures of merit : the method was linear in the concentration range between 0.781 and 500 μg/mL (linear regression coefficient 0.9996), accuracy was between 99.3% and 100.9%, intra assay precision was between 0.3% and 1.0% and intermediate precision was between 1.0% and 2.1%. Evaluation of the specificity of the method showed no interference between excipients or products of force degradation and BUS. Under the selected conditions, separation of BUS and its d...
A high-performance liquid chromatographic (HPLC) method has been developed for the separation and... more A high-performance liquid chromatographic (HPLC) method has been developed for the separation and determination of S- and R-enantiomers of betaxolol in tablets and ophthalmic preparations. Baseline resolution was achieved by using teicoplanin macrocyclic antibiotic chiral stationary phase (CSP) known as Chirobiotic T with fluorescence detection at excitation/emission wavelengths 275/305 nm. The polar ionic mobile phase (PIM) consists of methanol-glacial acetic acid-triethylamine, (100:0.020:0.025, v/v/v) has been used at a flow rate of 1.5 ml/min. All analytes with S-(-)-atenolol as internal standard were conducted at ambient temperature. The method is highly specific where another coformulated compounds did not interfere. The stability of betaxolol enantiomers under different degree of temperature also studied. The results showed that it is stable for at least 7 days at 70 degrees C. The method validated for its linearity, accuracy, precision and robustness. Experimental design was...
MEEKC electropherograms of (A) a standard mixture of (2.0 μg mL−1) HCT, (1), DEX-SP, (2), and DEX... more MEEKC electropherograms of (A) a standard mixture of (2.0 μg mL−1) HCT, (1), DEX-SP, (2), and DEX, (3) and (B) the treated rabbit plasma sample.
A novel method was developed for the simultaneous determination of guaifenesin (GUA) and ketorola... more A novel method was developed for the simultaneous determination of guaifenesin (GUA) and ketorolac tromethamine (KET) enantiomers in plasma samples. Since GUA probably increases the absorption of coadministered drugs (e.g., KET), it would be extremely important to monitor KET plasma levels for the purpose of dose adjustment with a subsequent decrease in the side effects. Enantiomeric resolution was achieved on a polysaccharide-based chiral stationary phase, amylose-2, as a chiral selector under the normal phase (NP) mode and using ornidazole (ORN) as internal standard. This innovative method has the advantage of the ease and reliability of sample preparation for plasma samples. Sample clean-up was based on simply using methanol for protein precipitation followed by direct extraction of drug residues using ethanol. Both GUA and KET enantiomers were separated using an isocratic mobile phase composed of hexane/isopropanol/trifluoroacetic acid, 85:15:0.05 v/v/v. Peak area ratios were linear over the range 0.05-20 µg/mL for the four enantiomers S (+) GUA, R (-) GUA, R (+) KET, and S (-) KET. The method was fully validated according to the International Conference on Harmonization (ICH) guidelines in terms of system suitability, specificity, accuracy, precision, robustness, and solution stability. Finally, this procedure was innovative to apply the rationale of developing a chiral high-performance liquid chromatography (HPLC) procedure for the simultaneous quantitative analysis of drug isomers in clinical samples.
A novel, fast, sensitive, and specific capillary electrophoresis (CE) technique coupled to a diod... more A novel, fast, sensitive, and specific capillary electrophoresis (CE) technique coupled to a diode array detector has been developed for the separation and simultaneous determination of carvedilol (CRV) and hydrochlorothiazide (HCT) in two combination formulations. The proposed method utilized a fused silica capillary (55 cm × 75 μm id) and the background electrolyte solution phosphate buffer (12.5 mM, pH 7.4)–methanol (95 + 5, v/v). The separation was achieved at 30 kV applied voltage and 24°C. Atorvastatin (80 μg/mL) was chosen as the internal standard. The described method was linear over the range of 1–200 and 0.2–150 μg/mL for CRV and HCT, respectively. Intraday and interday RSD (n = 6) was ≤1.4%. The LOD values of CRV and HCT were 0.26 and 0.07 μg/mL, respectively. The validated CE method was successfully applied to the analysis of two commercial tablet dosage forms. Forced degradation studies were performed on bulk samples of the two drugs using thermal, photolytic, hydrolyti...
Enantiomeric resolution of atenolol was achieved on the HPLC vancomycin macrocyclic antibiotic ch... more Enantiomeric resolution of atenolol was achieved on the HPLC vancomycin macrocyclic antibiotic chiral stationary phase Chirobiotic V. The polar ionic mobile phase consisted of methanol–glacial acetic acid–triethylamine (100 + 0.025 + 0.75, v/v/v) at a flow rate of 0.8 mL/min. Fluorescence detection at 275/305 nm for excitation and emission, respectively, was used. Plasma samples were purified using SPE on Oasis HLB cartridges. The calibration curves in plasma were linear over the range of 5–400 ng/mL (r = 0.999) for each enantiomer with an LOD of 1.0 ng/mL. The proposed method was validated in compliance with International Conference of Harmonization guidelines in terms of linearity, accuracy, precision, LOD, LOQ, and selectivity. The overall recoveries for S-(–)- and R-(+)-atenolol enantiomers from plasma were 95.0–99.5%; RSD ranged from 2.5 to 3.3%. The developed method was applied for the trace analysis of atenolol enantiomers in plasma and for the pharmacokinetic investigation o...
Uploads
Papers by Mona Alshehri