Synthesis of new analgesics based on 4-isopropyl-1-phenyl-3-(trifluoromethyl)pyrazol-5-one

Methyl 4-trifluoro-2-isopropyl-4-oxobutanoate prepared by the improved procedure was cyclized with hydrazines to afford the title pyrazole derivatives. N- and O-alkylation of 4-isopropyl-1-phenyl-3-(trifluoromethyl)pyrazol-5-ol gave trifluoromethyl analogues of Propyphenazone and 5-alkoxy derivatives. 4-Isopropylpyrazoles containing O-butoxy moiety with a terminal trifluoromethyl or acyloxy group were found to demonstrate a promising analgesic activity.     

VUV photon‐induced ionization/dissociation of antipyrine and propyphenazone: mass spectrometric and theoretical insights

Two analgesic and anti‐inflammatory drugs, antipyrine and propyphenazone, were investigated with infrared laser desorption/tunable synchrotron vacuum ultraviolet (VUV) photoionization mass spectrometry (IR LD/VUV PIMS) and theoretical calculations. Mass spectra of the two drugs were measured at various photon energies. Fragment ions were gradually produced as photon energy increases. The structural assignment of the dominant fragment ions was supported by the results from a commercial electron impact time‐of‐flight mass spectrometer (EI‐TOF MS). Primary fragmentation pathways were established from experimental observations combining with theoretical calculations. Methyl radical elimination is a common fragmentation pathway for two analytes. However, for propyphenazone cation, isopropyl group elimination to form antipyrine cation is another competitive pathway. Copyright © 2010 John Wiley & Sons, Ltd.     

Simultaneous Determination of Paracetamol, Caffeine and Propyphenazone in Pharmaceuticals by Means of a Single Flow-Through UV Multiparameter Sensor

 For the first time, a multiparameter-responding flow-through system with solid phase UV spectrophotometric detection (a multiparameter optosensor) is described for the simultaneous determination of a mixture of three active principles (paracetamol, caffeine and propyphenazone) using univariate calibration. Quantitation is based on the direct intrinsic UV absorbance measurements of the analytes when they reach the sensing zone (C₁₈ silicagel) placed in the flow cell of the FIA system. Because of the strong spectral overlap showed by these analytes, a temporary sequentiation in their arrival to the sensing zone is required from one only injection. It is achieved by means of an on-line simultaneous retention of two of them (caffeine and propyphenazone) on a minicolumn filled with C₁₈ silica-gel placed before the solid phase UV transductor, while paracetamol passes through the minicolumn and develops its transitory signal. Then, caffeine and propyphenazone are successively eluted from the column using two different methanol/water solutions (10% and 50% v.v respectively) and reach sequentially the sensing zone, developing their respective signals. Thus, with a single injection very good linear responses were obtained in the ranges 25–350 (paracetamol), 5–75 (caffeine) and 15–150 (propyphenazone) μg mL⁻¹. Detection limits ranging from 0.65 to 7.5 μg mL⁻¹ were found. Application of the detector to the successfully determination of the analytes in commercial pharmaceuticals was demonstrated. Correspondence: Department of Physical and Analytical Chemistry, Faculty of Experimental Sciences, University of Jaén, Paraje Las Lagunillas, E-23071 Jaén, Spain. e-mail: amolina@ujaen.es Received June 15, 2002; accepted November 12, 2002     

The Second-Derivative Spectrophotometric Assay of a Multicomponent Analgetic Mixture

In this paper the second-derivative spectrophotometric method for the simultaneous determination of some analgetic ingredients was described. Optimal conditions for the quantitative analysis of the three-component analgetic mixture of Dalivon® tablets were settled. The second-derivative order of the spectra in sodium hydroxide with the wavelength modulation was used. For the determination of paracetamol the “zero-crossing” technique was applied, but for propyphenazone and caffeine the characteristic peak amplitude had to be corrected.

The authors propose this second-derivative spectrophotometry for a rapid, simple, precise and accurate determination of the Dalivon® tablets or a corresponding multicomponent mixture.     

Determination of caffeine in solid pharmaceutical samples by FTIR spectroscopy

Fourier transform infrared spectroscopy has been used for the quantitative determination of caffeine in several pharmaceutical products: acetyl salicylic acid, paracetamol and propyphenazone. The method is simple, rapid and selective, and allows the determination of caffeine without sample pretreatment and without separation from the matrix. Two techniques for measuring the infrared spectra of caffeine are described: transmission through pellets and diffuse reflectance from powder (DRIFT). In both methods, samples were diluted (1%) with KBr. Caffeine in pharmaceutical matrices was recovered within 5% error in pellets and 10% by DRIFT. Relative standard deviations were generally 1.5% for repeated measurements on a single pellet and 5% for measurements on different pellets. DRIFT in the vacuum mode gave rather large RSDs. The limit of detection of the pellet technique was about 0.5% caffeine in the original sample.