Saeeda Nadir Ali

An Ultra-Sensitive LC Method for Simultaneous Determination of Rosuvastatin, Alprazolam and Diclofenac Sodium in API, Pharmaceutical Formulations and Human Serum by Programming the Detector

Here, we report a rapid and efficient liquid chromatographic method with UV detection for the simultaneous determination of rosuvastatin, alprazolam and diclofenac sodium in API, pharmaceutical formulations and human serum employing a reversed phase Bondapak C18 (25 cm, 0.46 cm, 10 μm) column at room temperature using methanol: water (80:20 v/v) and pH adjusted to 2.9 with 85% o-phosphoric acid. Separation was achieved within a time span of 6 min. The detector response was monitored at 240 nm and the flow rate was set at 1.0 mL.min -1 . Various LC parameters were optimized and developed method was validated as per ICH (2006) guidelines. Linear calibration range was determined to be 0.02-0.64, 0.125-4.0 and 0.05-1.6 μg.mL -1 and detection and quantitation limits were found to be 4.0, 17.0, 7.0 and 12.0, 52.0, 22.0 ng.mL-1 for rosuvastatin, alprazolam and diclofenic sodium respectively. Method was linear for all analytes with correlation coefficients >0.998. The intra-day and inter-day accuracy and precision of the assay were in acceptable range of 98.21-101.91% recovery and 0.20-2.07% RSD. The sensitivity of the method was enhanced when the chromatograms were analyzed by programming the detector at individual λmax of 244, 222 and 284 nm for rosuvastatin, alprazolam and diclofenac sodium respectively. High peak intensity was observed on injecting same sample concentration after the detector was programmed. Linearity was obtained even at lower concentrations of 0.02-0.64, 0.05-1.60 and 0.02-0.64 μg.mL -1 . LOD and LOQ values shifted down to 3.0, 6.0, 1.0 and 9.0, 19.0, 3.0 ng.mL -1 respectively. Recovery was found to be in the range of 98.32-101.87% and inter-day and intra-day precision was less than 2.10%. The proposed method was found to be robust and successfully employed for the determination of studied drugs in commercial formulations and human serum without interference of excipients or endogenous components of serum.

Simultaneous Liquid Chromatographic Determination of Two Co- Prescribed Anti-Cancer Drugs in Bulk Drug, Dosage Formulations and in Human Serum Using Multivariate Technique: Application to in vitro Drug Interaction

Present study describes the development and validation of a high-performance liquid chromatographic (HPLC) assay for the simultaneous quantification of atorvastatin and celecoxib in human serum and pharmaceutical formulations. The separation was carried out on Bondapak, C18 (10 μm, 25×0.46 cm) column using mobile phase 80:20 methanol-water of pH 3.5, maintained with o-phosphoric acid. The method was optimized using multivariate technique and detector response was recorded at five different wavelengths. Chromatography was performed at ambient temperature by pumping the mobile phase at a flow rate of 1.0 mL min-1. Calibration curves were found to be linear with correlation coefficient greater than 0.998 over the concentration range 2-60 and 2-70 ng mL-1 with detection limits 0.024 and 0.019 ng mL-1 in bulk drug and 0.04 and 0.01 ng mL-1 in serum at isobestic point. The method was validated for specificity, selectivity, and linearity, accuracy, precision and intermediate precision. The proposed method is valid for the determination of drugs in pharmaceutical formulations without interference of excipients. Recovery values of both drugs were 99.33 to 101.65%. Moreover the in vitro interaction studies of atorvastatin in presence of celecoxib were carried out at physiological temperature (37°C), simulating stomach environment and the reactions were studied by RP-HPLC.

Spectrophotometric Determination of Quinolones by Charge Transfer Complexation with Chloranilic Acid: Synthesis and Characterization

A simple and sensitive spectrophotometric method has been described for the assay of quinolones in bulk drug and in pharmaceutical formulations. The developed method is based on the formation of colored charge transfer complexes of quinolones with chloranilic acid in acetonitrile solvent. The formed complexes absorbed at 417, 436, 419 and 436 nm for sparfloxacin, enoxacin, norfloxacin and levofloxacin respectively. Beers law is obeyed in the concentration range of 0.5-7, 1-10, 1-10 and 1-5 µg mL -1 with LLOD values 0.036, 0.0041, 0.0344 and 0.0063 ng mL-1 respectively. The data are discussed in terms of molar absorptivity, association constant and Gibbs free energy. Spectral characteristics including oscillators strength, dipole moment, ionization potential, energy of complexes and resonance energy have been determined. Benesi-Hildebrand plots for each complex have been constructed. Structural characteristics of synthesized charge transfer complexes were determined by IR spectroscopy. The applicability of the method was demonstrated by determination of studied drugs in commercial tablets with satisfactory results. No interference from excipients was observed in the formulation.

The Use of Chloranilic Acid for the Spectrophotometric Determination ofThree Macrolides through Charge Transfer Complex

In the present study, simple and fast spectrophotometricmethod have been reported for the determination of three macrolides i.e., erythromycin, roxithromycin and clarithromycin through charge transfer complexes. The method involves the interaction of macrolides with chloranilic acid in acetonitrile medium. Stoichiometry was found to be 1:1 for all the complexes. Under the optimizedconditions, the complexes were found to be absorbed at 498, 496 and 491 nm with in the linearity range of 3-36, 4-40 and 8-40 μg mL -1 with minimum detection limit 190, 600 and 370 ng mL -1 for respectively. The corresponding molar absorptivity values were determined to be 2.07×10 4 , 1.81×10 4 and 1.67×10 4 Mol -1 cm -1 respectively. The data is discussed in terms of oscillator’s strength, dipole moment, ionization potential, energy of complexes, resonance energy, association constant and Gibb’s free energy changes. Benesi- Hildebrand plots for all complexes have been constructed. Furthermore, the methods were successfully applied for the determination of studied macrolides in pharmaceutical formulations. The interday and intraday precision and percent recovery values were evaluated. Results of analysis were validated successfully. Commonly present excipients did not show interference during analysis

Synthesis and Spectrophotometric Determination Ibuprofen Charge Transfer Complexes with P-Chloranil, 7,7,8,8-Tetracyanoquinodimethane,Bromothymol Blue, Methyl Orange and Picric Acid

Three simple, sensitive and inexpensive spectrophotometric methods have been described for the assay of ibuprofen in bulk drugs and pharmaceutical formulations. The developed methods are based on the formation of colored charge transfer complexes of ibuprofen with p-chloranil, 7,7,8,8-tetracyanoquinodimethane, bromothymol blue, methyl orange and picric acid in acetonitrile as solvent. These newly formed complexes were found to absorb at 438, 394, 403, 418, 374 nm respectively. Optimizations of various experimental conditions are described. Beer’s law obeyed in the concentration range6-54, 2-24, 4-28, 3-21 and 4-28 μgmL-1 with correlation coefficient >0.998 in each case and lower limit of detection values were 76, 90, 234, 63 and 189 ng mL-1, respectively. The association constants and standard free energy changes were studied using Benesi-Hildebrand plots. Oscillator’s strength, ionization potential and energy of complexes in the ground state for all the complexes have been calculated. For further confirmation, solid charge transfer complexes were synthesized and characterized by IR and 1H-NMR spectroscopy. The applicability of the method was demonstrated by the determination of studied drugs in commercial tablets with satisfactory results. No interference from excipients was observed in the formulations.

Charge Transfer Complexes of Gamma Aminobutyric Acid-Analogue, A Neurotransmitter: Synthesis and Spectrophotometric Determination

Here, we report spectrophotometric method for the determination of gabapentin through charge transfer complexes with σ and π acceptors and also with dye stuffs. The method involves ion-pair complex formation of gabapentin with ninhydrin, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, tetracyanoethylene, methyl orange and picric acid. The optimum conditions for the reactions and validation of described procedure have been studied. Resulting complexes absorb at 580, 315, 340, 464 and 342 nm in the Beer’s law range of 2-22, 32-80, 40-360, 12-96 and 15-135 μg mL-1 with correlation coefficient greater than 0.998 in each case respectively. The proposed method was applied successfully for the determination of gabapentin in pharmaceutical formulations. Satisfactory recovery values suggest that the method is reliable for the determination of gabapentin in pharmaceutical formulations without interference of excipients. In addition, the spectral characteristics including oscillator’s strength, dipole moment, ionization potential, energy of complexes, resonance energy and also the thermodynamic parameters i.e. association constant and Gibb’s free energy changes have been determined. Benesi-Hildebrand plots for each complex have been constructed. Further, solid charge transfer complexes of gabapentin were synthesized and characterized by IR spectroscopy.

Liquid chromatographic method for the simultaneous determination of captopril, piroxicam, and amlodipine in bulk drug, pharmaceutical formulation, and human serum by programming the detector.

A highly sensitive LC method with UV detection has been developed for the simultaneous determination of coadministered drugs captopril, piroxicam, and amlodipine in bulk drug, pharmaceutical formulations, and human serum at the isosbestic point (235 nm) and at individual λmax (220, 255, and 238 nm, respectively) by programming the detector with time to match the individual analytes chromophore, which enhanced the sensitivity with linear range. The assay involved an isocratic elution of analytes on a Bondapak C18 (10 μm, 25 × 0.46 cm) column at ambient temperature using a mobile phase of methanol/water 80:20 at pH 2.9 and a flow rate of 1.0 mL/min. Linearity was found to be 0.25-25, 0.10-6.0, and 0.20-13.0 μg/mL with correlation coefficient >0.998 and detection limits of 7.39, 3.90, and 9.38 ng/mL, respectively, whereas calibration curves for wavelength-programmed analysis were 0.10-6.0, 0.04-2.56, and 0.10-10.0 μg/mL with correlation coefficient >0.998 and detection limits of 5.79, 2.68, and 3.87 ng/mL, respectively. All the validated parameters were in the acceptable range. The recovery of drugs was 99.32-100.39 and 98.65-101.96% in pharmaceutical formulation and human serum, respectively, at the isosbestic point and at individual λmax . This method is applicable for the analysis of drugs in bulk drug, tablets, serum, and in clinical samples without interference of excipients or endogenous serum components.

Ultra Sensitive Liquid Chromatographic Method for the Simultaneous Determination of Carbamazepine with Nsaids in API, Pharmaceutical Formulation and Human Serum by Programming the Detector: Application to In Vitro Drug Interaction

Here we describe an ultra-sensitive reverse phase liquid chromatographic method for the simultaneous determination of carbamazepine with NSAIDs in API, pharmaceutical formulation and human serum with UV detection. The separation of these multiple drug components was made by a Bondapak C18 column (10 µm, 25 cm×0.46 cm) using a moderate acidic mixture of mobile phase i.e., methanol:water 80:20 with pH adjusted to 3.0 using 85% o-phosphoric acid. The flow rate of the mobile phase was affixed at 1.0 ml min -1 for the best minimum interval of elusion of all the analytes. The detector response was monitored at isobestic point of 220 nm at ambient temperature. Calibration curves were obtained in the range of 0.4-12 µg mL -1 for carbamazepine, 0.5-16 µg mL -1 for meloxicam and 0.25-8.0 µg mL -1 for ibuprofen and mefenamic acid. Limits of detection were found to be 4.0, 3.0, 1.0, and 13.0 ng mL-1 respectively. The method was compared by programming the detector at individual wavelength of components which showed more sensitivity with linear range 0.10-3.0, 0.15-5.0, 0.10-3.0 and 0.125-4.0 µg mL -1 and detection limits 2.0, 2.0, 1.0, and 3.0 ng mL-1 respectively. ICH guidelines were followed for validation study. The method showed good precision and accuracy within acceptable range and can be successfully applied for the determination of these drugs in pharmaceutical formulations, human serum and clinical laboratories without interference of excipients or endogenous components of serum. In vitro interaction studies have also been carried out at physiological temperature in buffers of various pH (4, 7.4 and 9.0) simulating human stomach environments and % availability has been calculated. Moreover, the solid charge transfer complexes of carbamazepine with interacting NSAIDs were synthesized and characterized by IR spectroscopy and verified by computational molecular modeling.

Spectrophotometric Studies of Lamotrigine Charge Transfer Complexes: Synthesis and Characterization

Charge transfer complexes of lamotrigine with 7,7,8,8-tetracyanoquinodimethane, bromothymol blue and picric acid have been investigated by spectrophotometric method. Optimum conditions for the reactions and validation data is reported. Resulting complexes absorb at 394, 404 and 374 nm in the Beers law range of 0.15-15, 0.25- 10 and 3.0-18 µg mL -1 with correlation coefficient greater than 0.998 in each case and detection limits 45, 47 and 57 µg mL -1 respectively. The data are discussed in terms of molar absorptivity, association constant and Gibbs free energy. Spectral characteristics including oscillators strength, dipole moment, ionization potential, energy of complexes and resonance energy have been determined. Benesi-Hildebrand plots for each complex have been constructed. The proposed method was applied successfully for the determination of lamotrigine in pharmaceutical formulations. Satisfactory recovery values suggested that the method is reliable for the determination of lamotrigine in pharmaceutical formulations without interference of excipients. Further, solid charge transfer complexes were synthesized and characterized by IR and 1 H NMR spectroscopy.