Development of Dioctyl Phthalate@Fe3O4 Nanocomposite Reinforced Hollow Fiber Solid/ Liquid Phase Microextraction Followed by HPLC-DAD for the Determination of Atorvastatin and Gemfibrozil in Human Urine.

BACKGROUND: The desirable levels of lipids, especially in patients with coronary artery disease, might not be achievable with a single lipid-lowering drug; thus, combination therapy using atorvastatin and gemfibrozil seems to be a promising approach. However, the potential for drugdrug interaction needs to be taken into consideration, and the combination (atorvastatin and gemfibrozil) is recommended only when other options for reducing lipids have been exhausted. OBJECTIVES: Many studies are conducted for the determination of atorvastatin or gemfibrozil in biological fluids and tablets; however, the simultaneous determination of the two drugs in complex biological matrices is limited. Consequently, the development of a sensitive method for simultaneous determination of atorvastatin and gemfibrozil in urine samples is urgently needed to make sure that the doses of both medications are given to patients correctly to prevent the risk of side effects outcomes associated with the adverse drug-drug interaction. METHODS: A synthesized nanocomposite sorbent, dioctyl phthalate coated on the surface of magnetite (DOP@Fe3O4), was reinforced and immobilized into the pores of 2.5 cm segment hollow fiber microtube via ultrasonication, and the lumen of the microtube was filled with 1-octanol as an organic solvent with two ends heat-sealed. The prepared (DOP@Fe3O4-HF-SLPME) device was directly immersed into 10 mL of a sample solution containing atorvastatin and gemfibrozil with agitation. Subsequently, the microextraction device was transferred to HPLC-micro-vial containing an appropriate solvent, and the selected analytes were desorbed under ultrasonication prior to HPLCDAD analysis. The main factors influencing the adsorption and desorption process of the selected drugs have been optimized. RESULTS: The DOP@Fe3O4-HF-SLPME combined with the HPLC-DAD method was analytically evaluated for the simultaneous determination of atorvastatin and gemfibrozil in human urine samples using the optimized conditions. In spiked urine samples, the method showed a good linearity R2˃ 0.998, RSD from 1.41- 5.33%, and the limits of detection/ quantification (LOD/ LOQ) were 0.11/ 0.36 and 0.73/ 2.42 µg L-1 for atorvastatin and gemfibrozil, respectively. The enrichment factors of atorvastatin and gemfibrozil were 83.4 and 101.2, with extraction recoveries of 80.9% and 99.0%, respectively. The developed method demonstrated comparable results against referenced methods and a satisfactory result for determining the selected drugs in the patient's urine samples. CONCLUSION: The DOP@Fe3O4-HF-SLPME followed by HPLC-DAD was proved to be an efficient, sensitive, and cost-effective biopharmaceutical analysis method for trace levels of atorvastatin and gemfibrozil in the biological fluid matrix.

Multi-walled Carbon Nanotubes Reinforced into Hollow Fiber by Chitosan Sol-gel for Solid/Liquid Phase Microextraction of NSAIDs from Urine Prior to HPLC-DAD Analysis.

BACKGROUND: The efficient analytical method for the analysis of nonsteroidal antiinflammatory drugs (NSAIDs) in a biological fluid is important for determining the toxicological aspects of such long-term used therapies. METHODS: In the present work, multi-walled carbon nanotubes reinforced into a hollow fiber by chitosan sol-gel assisted-solid/ liquid phase microextraction (MWCNTs-HF-CA-SPME) method followed by the high-performance liquid chromatography-diode array detection (HPLC-DAD) was developed for the determination of three NSAIDs, ketoprofen, diclofenac, and ibuprofen in human urine samples. MWCNTs with various dimensions were characterized by various analytical techniques. The extraction device was prepared by immobilizing the MWCNTs in the pores of 2.5 cm microtube via chitosan sol-gel assisted technology while the lumen of the microtube was filled with few microliters of 1-octanol with two ends sealed. The extraction device was operated by direct immersion in the sample solution. RESULTS: The main factors influencing the extraction efficiency of the selected NSAIDs have been examined. The method showed good linearity R2 ≥ 0.997 with RSDs from 1.1 to 12.3%. The limits of detection (LODs) were 2.633, 2.035 and 2.386 µg L-1, for ketoprofen, diclofenac, and ibuprofen, respectively. The developed method demonstrated a satisfactory result for the determination of selected drugs in patient urine samples and comparable results against reference methods. CONCLUSION: The method is simple, sensitive and can be considered as an alternative for clinical laboratory analysis of selected drugs.

A comparative study of first-derivative spectrophotometry and column high-performance liquid chromatography applied to the determination of repaglinide in tablets and for dissolution testing.

A fast and reliable method for the determination of repaglinide is highly desirable to support formulation screening and quality control. A first-derivative UV spectroscopic method was developed for the determination of repaglinide in tablet dosage form and for dissolution testing. First-derivative UV absorbance was measured at 253 nm. The developed method was validated for linearity, accuracy, precision, limit of detection (LOD), and limit of quantitation (LOQ) in comparison to the U.S. Pharmacopeia (USP) column high-performance liquid chromatographic (HPLC) method. The first-derivative UV spectrophotometric method showed excellent linearity [correlation coefficient (r) = 0.9999] in the concentration range of 1-35 microg/mL and precision (relative standard deviation < 1.5%). The LOD and LOQ were 0.23 and 0.72 microg/mL, respectively, and good recoveries were achieved (98-101.8%). Statistical comparison of results of the first-derivative UV spectrophotometric and the USP HPLC methods using the t-test showed that there was no significant difference between the 2 methods. Additionally, the method was successfully used for the dissolution test of repaglinide and was found to be reliable, simple, fast, and inexpensive.

Iminopropadienones from dioxanediones, isoxazolopyrimidinones, pyridopyrimidinones, and pyridopyrimidinium olates.

Iminopropadienones, RN=C=C=C=O, can be generated from four different types of precursors in flash vacuum thermolysis reactions: 1,3-dioxane-4,6-diones 1, isoxazolopyrimidinones 2, pyridopyrimidinium olates 3, and pyridopyrimidinones 4. 2,6-Difluorophenyl-, 2,6-diethylphenyl-, o-tert-butylphenyl-, and mesityliminopropadienone have been directly observed by Ar matrix IR spectroscopy in one or more of these reactions. Reactions with bis-nucleophiles afford pyridopyrimidinones and perhydrodiazepinone derivatives.

Chemistry of stable iminopropadienones, RN=C=C=C=O.

The synthesis, spectroscopic properties, and chemical reactions of the stable (neopentylimino)-, (mesitylimino)-, and (o-tert-butylphenylimino)propadienones (6) are reported. Nucleophilic addition of amines affords the malonic amidoamidines 7 and 8. 3,5-Dimethylpyrazole reacts analogously to form 9b. Addition of 1,2-dimethylhydrazine produces pyrazolinones 10-12. Addition of N,N'-dimethyldiaminoethane, -propane, and -butane gives diazepine, diazocine, and diazonine derivatives 13-15, respectively (X-ray structures of 13c, 14a, and 15a are available). The mesoionic pyridopyrimidinium olates 18 are obtained by addition of 2-(methylamino)pyridine (X-ray structure of 18b available). Primary 2-aminopyridines afford the pyridopyrimidininones 20-29 and 31 (X-ray structure of 21a available), and 2-aminopyrimidines and 2-aminopyrazine afford pyrimidopyrimidinones and pyrazinopyrimidinones 33-35. Pyrimidoisoquinolinone 36 results from 1-aminoisoquinoline and pyridoquinolinone 40 from 8-aminoquinoline. 2-Aminothiazoline and 2-aminothiazole afford thiazolopyrimidinone derivatives 41-43 (X-ray structure of 43a available).