Journal of Liquid Chromatography & Related Technologies, Jan 8, 2014
ABSTRACT An artificial neural network (ANN) was employed to model the chromatographic response su... more ABSTRACT An artificial neural network (ANN) was employed to model the chromatographic response surface for the isocratic separation of binary mixtures of diflunisal (DFL) and naproxen (NAP). The two drugs were separated using RP-HPLC and detected with a photodiode array detector (HPLC-DAD). The ANN was trained using the composition of the mobile phase including the percentage of acetonitrile in the mobile phase and the pH of the aqueous phase as input variables while the capacity factors were used as the output variables. ANN was trained to accurately describe the retention factors of each of DFL and NAP within a defined experimental space of aqueous phase pH 2.7–5.8 and 38–60% acetonitrile in the mobile phase. Using the best performing ANN, the optimum conditions predicted were 0.05 M sodium dihydrogenphosphate aqueous solution adjusted to pH 3.4 and acetonitrile in a ratio of (50: 50, v/v). The optimized conditions were used to develop a stability-indicating HPLC method for the quantitative determination of DFL and NAP in tablet dosage forms. The drugs were subjected to oxidation, hydrolysis, photolysis, and heat to apply stress conditions. Complete separation was achieved for the parent compounds and all degradation products. The method was validated according to ICH guidelines.
Chemometrics and Intelligent Laboratory Systems, Dec 1, 2008
This manuscript discusses the application of chemometrics to the polarographic response data. It ... more This manuscript discusses the application of chemometrics to the polarographic response data. It deals with convolution of signals using orthogonal polynomials in the determination of multi-component mixtures. The method was found beneficial in the resolution of partially ...
Journal of Pharmaceutical and Biomedical Analysis, May 1, 2016
A sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry method... more A sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry method has been developed and validated for the simultaneous analysis of selected tyrosine kinase inhibitors (TKIs)(gefitinib GEF, erlotinib ERL), corticosteroids (dexamethasone DEX, prednisolone PRED), and the antiemetic ondansetron (OND) in rat plasma samples. After the addition of domperidone (DOM) as internal standard (IS), spiked plasma samples were prepared using the solid phase extraction (SPE) C 18 cartridges. Chromatographic separation was performed on a Waters BEH C18 column with an isocratic elution using a mobile phase composed of acetonitrile and water, each with 0.1% formic acid, (80: 20, v/v), at a flow rate of 0.2mL/min. Quantitation of the analytes was performed using the multiple reaction monitoring (MRM) mode with the positive ionization mode at m/z 447.25>128.08 (GEF), m/z 394.20>278.04 (ERL), m/z 393.30>147.04 (DEX), m/z 361.29>147.02 (PRED), m/z 294.18>170.16 (OND), and m/z 426.26>175.07 (DOM). The method was validated over the concentration range of 0.025-100 (GEF, ERL, OND) and 0.05-100ng/mL plasma (PRED, DEX) with very low lower limit of quantification of 0.025 (GEF, ERL, OND) and 0.05ng/mL (DEX, PRED). The intra- and inter-day precision (RSD%) evaluated at four different concentration levels were within the acceptable limits (<15%). The method provided good extraction recovery of all analytes from rat plasma (Er% from -14.05 to -1.08). The validated method was successfully applied to the pharmacokinetic studies following the oral administration of selected combinations of the studied drugs. This study can be readily applied in therapeutic drug monitoring (TDM) in patients receiving these drug combinations as well as investigation of possible drug interactions between TKIs and DEX/PRED/OND.
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Oct 1, 2008
A new spectrophotometric method was developed for the simultaneous determination of ternary mixtu... more A new spectrophotometric method was developed for the simultaneous determination of ternary mixtures, without prior separation steps. This method is based on convolution of the double divisor ratio spectra, obtained by dividing the absorption spectrum of the ternary mixture by a standard spectrum of two of the three compounds in the mixture, using combined trigonometric Fourier functions. The magnitude of the Fourier function coefficients, at either maximum or minimum points, is related to the concentration of each drug in the mixture. The mathematical explanation of the procedure is illustrated. The method was applied for the assay of a model mixture consisting of isoniazid (ISN), rifampicin (RIF) and pyrazinamide (PYZ) in synthetic mixtures, commercial tablets and human urine samples. The developed method was compared with the double divisor ratio spectra derivative method (DDRD) and derivative ratio spectra-zero-crossing method (DRSZ). Linearity, validation, accuracy, precision, limits of detection, limits of quantitation, and other aspects of analytical validation are included in the text.
Gas chromatography with infrared detection (GC-IRD) provides direct confirmatory data for the ide... more Gas chromatography with infrared detection (GC-IRD) provides direct confirmatory data for the identification of the psychoactive designer drug 3-trifluoromethylphenylpiperazine (3-TFMPP) from the regioisomeric 2- and 4-trifluoromethylphenylpiperazines. These three regioisomeric substances are well resolved by GC and the vapor phase infrared spectra clearly differentiate among the three trifluoromethylphenyl substitution patterns. However, the mass spectra for the three regioisomeric 2-, 3-, and 4-trifluoromethylphenylpiperazines are identical and do not provide structural confirmation for one of the three isomers to the exclusion of the other two compounds. Perfluoroacylation of the secondary amine nitrogen for each of the three regioisomers was conducted in an effort to individualize their mass spectra. The resulting derivatives were resolved by GC and their mass spectra showed some differences in relative abundance of fragment ions without the appearance of any unique fragments for specific confirmation of structure.
Journal of Liquid Chromatography & Related Technologies, Jan 8, 2014
ABSTRACT An artificial neural network (ANN) was employed to model the chromatographic response su... more ABSTRACT An artificial neural network (ANN) was employed to model the chromatographic response surface for the isocratic separation of binary mixtures of diflunisal (DFL) and naproxen (NAP). The two drugs were separated using RP-HPLC and detected with a photodiode array detector (HPLC-DAD). The ANN was trained using the composition of the mobile phase including the percentage of acetonitrile in the mobile phase and the pH of the aqueous phase as input variables while the capacity factors were used as the output variables. ANN was trained to accurately describe the retention factors of each of DFL and NAP within a defined experimental space of aqueous phase pH 2.7–5.8 and 38–60% acetonitrile in the mobile phase. Using the best performing ANN, the optimum conditions predicted were 0.05 M sodium dihydrogenphosphate aqueous solution adjusted to pH 3.4 and acetonitrile in a ratio of (50: 50, v/v). The optimized conditions were used to develop a stability-indicating HPLC method for the quantitative determination of DFL and NAP in tablet dosage forms. The drugs were subjected to oxidation, hydrolysis, photolysis, and heat to apply stress conditions. Complete separation was achieved for the parent compounds and all degradation products. The method was validated according to ICH guidelines.
Chemometrics and Intelligent Laboratory Systems, Dec 1, 2008
This manuscript discusses the application of chemometrics to the polarographic response data. It ... more This manuscript discusses the application of chemometrics to the polarographic response data. It deals with convolution of signals using orthogonal polynomials in the determination of multi-component mixtures. The method was found beneficial in the resolution of partially ...
Journal of Pharmaceutical and Biomedical Analysis, May 1, 2016
A sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry method... more A sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry method has been developed and validated for the simultaneous analysis of selected tyrosine kinase inhibitors (TKIs)(gefitinib GEF, erlotinib ERL), corticosteroids (dexamethasone DEX, prednisolone PRED), and the antiemetic ondansetron (OND) in rat plasma samples. After the addition of domperidone (DOM) as internal standard (IS), spiked plasma samples were prepared using the solid phase extraction (SPE) C 18 cartridges. Chromatographic separation was performed on a Waters BEH C18 column with an isocratic elution using a mobile phase composed of acetonitrile and water, each with 0.1% formic acid, (80: 20, v/v), at a flow rate of 0.2mL/min. Quantitation of the analytes was performed using the multiple reaction monitoring (MRM) mode with the positive ionization mode at m/z 447.25>128.08 (GEF), m/z 394.20>278.04 (ERL), m/z 393.30>147.04 (DEX), m/z 361.29>147.02 (PRED), m/z 294.18>170.16 (OND), and m/z 426.26>175.07 (DOM). The method was validated over the concentration range of 0.025-100 (GEF, ERL, OND) and 0.05-100ng/mL plasma (PRED, DEX) with very low lower limit of quantification of 0.025 (GEF, ERL, OND) and 0.05ng/mL (DEX, PRED). The intra- and inter-day precision (RSD%) evaluated at four different concentration levels were within the acceptable limits (<15%). The method provided good extraction recovery of all analytes from rat plasma (Er% from -14.05 to -1.08). The validated method was successfully applied to the pharmacokinetic studies following the oral administration of selected combinations of the studied drugs. This study can be readily applied in therapeutic drug monitoring (TDM) in patients receiving these drug combinations as well as investigation of possible drug interactions between TKIs and DEX/PRED/OND.
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Oct 1, 2008
A new spectrophotometric method was developed for the simultaneous determination of ternary mixtu... more A new spectrophotometric method was developed for the simultaneous determination of ternary mixtures, without prior separation steps. This method is based on convolution of the double divisor ratio spectra, obtained by dividing the absorption spectrum of the ternary mixture by a standard spectrum of two of the three compounds in the mixture, using combined trigonometric Fourier functions. The magnitude of the Fourier function coefficients, at either maximum or minimum points, is related to the concentration of each drug in the mixture. The mathematical explanation of the procedure is illustrated. The method was applied for the assay of a model mixture consisting of isoniazid (ISN), rifampicin (RIF) and pyrazinamide (PYZ) in synthetic mixtures, commercial tablets and human urine samples. The developed method was compared with the double divisor ratio spectra derivative method (DDRD) and derivative ratio spectra-zero-crossing method (DRSZ). Linearity, validation, accuracy, precision, limits of detection, limits of quantitation, and other aspects of analytical validation are included in the text.
Gas chromatography with infrared detection (GC-IRD) provides direct confirmatory data for the ide... more Gas chromatography with infrared detection (GC-IRD) provides direct confirmatory data for the identification of the psychoactive designer drug 3-trifluoromethylphenylpiperazine (3-TFMPP) from the regioisomeric 2- and 4-trifluoromethylphenylpiperazines. These three regioisomeric substances are well resolved by GC and the vapor phase infrared spectra clearly differentiate among the three trifluoromethylphenyl substitution patterns. However, the mass spectra for the three regioisomeric 2-, 3-, and 4-trifluoromethylphenylpiperazines are identical and do not provide structural confirmation for one of the three isomers to the exclusion of the other two compounds. Perfluoroacylation of the secondary amine nitrogen for each of the three regioisomers was conducted in an effort to individualize their mass spectra. The resulting derivatives were resolved by GC and their mass spectra showed some differences in relative abundance of fragment ions without the appearance of any unique fragments for specific confirmation of structure.
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