Development of a novel UPLC approach to co-prediction of four active compounds in a multi-component pharmaceutical preparation.

In this work, a new ultra-performance liquid chromatography method based on photodiode array detection (UPLC-PDA) was first developed for the quantitative analysis of the quaternary mixture of ascorbic acid (AA), paracetamol (PAR), caffeine (CAF) and chlorpheniramine maleate (CPA) in a commercial dosage form. The developed UPLC-PDA method offered a new possibility for the co-determination of four active ingredients in a drug combination with short run time and simple sample preparation. The successful chromatographic separation of the four drugs was performed using a Waters Acquity UPLC BEH C18 column (1.7 µm 2.1 × 100 mm) (Mildford, USA) and a mobile phase consisting of water (12 %), acetonitrile (13 %) and 0.1 M H3PO4 (75 %) at a flow rate of 0.25 mL/min. The validation of the proposed UPLC-PDA approach was verified by analyzing synthetic mixtures, inter- and intra-day experiments, and commercial powder samples and provided satisfactory results.

Simultaneous determination of ascorbic acid and caffeine in commercial soft drinks using reversed-phase ultraperformance liquid chromatography.

A new reversed-phase ultraperformance liquid chromatography method with a photodiode array detector was developed for the quantification of ascorbic acid (AA) and caffeine (CAF) in 11 different commercial drinks consisting of one energy drink and 10 ice tea drinks. Separation of the analyzed AA and CAF with an internal standard, caffeic acid, was performed on a Waters BEH C18 column (100 mm × 2.1 mm, 1.7 µm i.d.), using a mobile phase consisting of acetonitrile and 0.2M H3PO4 (11:89, v/v) with a flow rate of 0.25 mL/min and an injection volume of 1.0 µL. Calibration graphs for AA and CAF were computed from the peak area ratio of AA/internal standard and CAF/internal standard detected at 244.0 nm and 273.6 nm, respectively. The developed reversed-phase ultraperformance liquid chromatography method was validated by analyzing standard addition samples. The proposed reversed-phase ultraperformance liquid chromatography method gave us successful results for the quantitative analysis of commercial drinks containing AA and CAF substances.

Continuous wavelet transform methods for the simultaneous determinations and dissolution profiles of valsartan and hydrochlorothiazide in tablets

ABSTRACT Continuous wavelet transform (CWT) was proposed for the simultaneous determination and dissolution profiles of valsartan (VAL) and hydrochlorothiazide (HCT) in tablets, without the use of a chemical separation procedure. The CWT approach was applied to the original UV spectra and their ratio spectra in the optimal wavelength ranges. After testing several wavelet families, Mexican hat function-CWT and Daubechies7-CWT (mexh-CWT and db7-CWT, respectively) were found to be suitable for the transformation of the original UV spectra. In the following procedure, mexh-CWT and Coiflets3-CWT (coif3-CWT) were found to be appropriate for the signal analysis of ratio spectra (RS) of VAL/HCT and HCT/VAL. Calibration graphs for VAL and HCT were obtained by measuring db7-CWT and mexh-CWT amplitudes in the transformation of the original absorption spectra and RS-coif-CWT and RS-mexh-CWT amplitudes in the transformation of the ratio spectra. The validity and applicability of the proposed CWT methods were evaluated through the analysis of an independent set of synthetic binary mixtures consisting of VAL and HCT. The proposed signal processing methods were then successfully applied to the simultaneous quantitative evaluation and simultaneous dissolution profiles of the related drugs in commercial tablets, with good agreement reported for the experimental results.

A chemometric optimization of method for determination of nitrosamines in gastric juices by GC-MS.

A chemometrically optimized isolation procedure combined with gas chromatography-mass spectrometry detection technique has been proposed for quantitative determination of trace levels of nitrosamines in gastric juice samples of patients with the gastrointestinal tract problems. The extraction conditions of each nitrosamine were optimized using regression modelling based on central composite design. The extraction conditions for all nitrosamines were selected to be 10.7 min for extraction time, 4.2 for pH and 23 for 2-propanol percentage in extraction solution. The obtained recoveries of nitrosamines ranged from 94.0 (NDMA) to 99.3 (NDPheA) %, and the precision of this method, as indicated by the relative standard deviations was within the range of 0.7 (NDPheA) and 2.6 (NDMA) %. The detection limits obtained from calculations by using GC-MS results based on S/N=3 were found within the range from 0.3 to 1.1 pg/mL. Total nitrosamine concentrations were found at the highest concentration up to 2431.12 pg/mL in cancer patients, whereas they were found at the lowest concentration down to 12.18 pg/mL in gastritis patients. The classification results of the gastric juice samples in different patient groups were very satisfactory, allowing 100% of patients to be correctly grouped. A new mathematical model has been developed allowing for the classification of gastric juices with a 93.1% success rate based on just the ratio of MNPIZ to DNPIZ. The ratio of MNPIZ to DNPIZ might be considered as a biomarker for the classification of gastric juices of patients and might act as an indicator of increased risk for stomach cancer.

A new application of continuous wavelet transform to overlapping chromatograms for the quantitative analysis of amiloride hydrochloride and hydrochlorothiazide in tablets by ultra-performance liquid chromatography.

A new application of continuous wavelet transform (CWT) to overlapping peaks in a chromatogram was developed for the quantitative analysis of amiloride hydrochloride (AML) and hydrochlorothiazide (HCT) in tablets. Chromatographic analysis was done by using an ACQUITY ultra-performance LC (UPLC) BEH C18 column (50 x 2.1 mm id, 1.7 pm particle size) and a mobile phase consisting of methanol-0.1 M acetic acid (21 + 79, v/v) at a constant flow rate of 0.3 mL/min with diode array detection at 274 nm. The overlapping chromatographic peaks of the calibration set consisting of AML and HCT mixtures were recorded rapidly by using an ACQUITY UPLC H-Class system. The overlapping UPLC data vectors of AML and HCT drugs and their samples were processed by CWT signal processing methods. The calibration graphs for AML and HCT were computed from the relationship between concentration and areas of chromatographic CWT peaks. The applicability and validity of the improved UPLC-CWT approaches were confirmed by recovery studies and the standard addition technique. The proposed UPLC-CWT methods were applied to the determination of AML and HCT in tablets. The experimental results indicated that the suggested UPLC-CWT signal processing provides accurate and precise results for industrial QC and quantitative evaluation of AML-HCT tablets.

Simultaneous spectrophotometric determination of cyproterone acetate and estradiol valerate in pharmaceutical preparations by ratio spectra derivative and chemometric methods.

Ratio spectra derivative spectrophotometry and two chemometric methods (classical least squares, CLS and inverse least squares, ILS, were proposed for the simultaneous quantitative analysis of a binary mixture consists of cyproterone acetate (CA) and estradiol valerate (EV) in the commercial pharmaceutical preparations. In the ratio spectra derivative method, linear regression equations for both drugs were obtained by measuring the analytical signals at the wavelenghts corresponding to either maximums and minimums in the first derivative spectra of the ratio spectra. In the chemometric techniques, the concentration matrix was prepared by using the synthetic mixtures containing these drugs. The absorbance matrix corresponding to the concentration matrix was obtained by measuring the absorbances at 14 wavelengths in the range 220-290 nm for the zero-order spectra. Two chemometric calibrations were constructed by using the absorbance matrix and concentration matrix for the prediction of the unknown concentrations of CA and EV in their mixture. The numerical values were calculated by using 'MAPLE V' software. The accuracy and the precision of the methods have been determined and they have been validated by analyzing synthetic mixtures containing these two drugs. The proposed methods were successfully applied to a pharmaceutical formulation, sugar-coated tablet, and the results were compared with each other.