A comparison of quantitative NMR and radiolabelling studies of the metabolism and excretion of Statil™ (3-(4-bromo-2-fluorobenzyl)-4-oxo-3H-phthalazin-1-ylacetic acid) in the rat

Application of Quantitative NMR in Pharmacological Evaluation of Biologically Generated Metabolites: Implications in Drug Discovery

“…We recently showed the value of conducting quantitative NMR studies in addressing metabolites in safety testing (Vishwanathan et al, 2009). The application of quantitative 19 F NMR in obtaining the mass balance of fluorinated compounds was demonstrated previously (Scarfe et al, 1998(Scarfe et al, , 1999Lenz et al, 2002;Duckett et al, 2006). The ability to quantitate microgram quantities of metabolites led us to further investigate the possibility of using quantitative NMR in accelerating the pharmacological evaluation of metabolites earlier in drug discovery.…”

Facile Synthesis and Structural Characterization of Some Phthalazin-1(2H)-one Derivatives as Antimicrobial Nucleosides and Reactive Dye

“…Similarly, heterocycles containing the phthalazine moiety are of interest because they show some pharmacological and biological activities [4][5][6]. Phthalazine derivatives were reported to possess anticonvulsant [7], antitumor [8], antihypertensive [9], antithrombotic [10], antidiabetic [11], antitrypanosomal [12], anti-inflammatory [13], cardiotonic [14] and vasorelaxant activities [15]. Therefore, number of methods have been reported for the synthesis of phthalazine derivatives [16][17][18][19][20][21][22].…”

Fluorine-19 nuclear magnetic resonance (19F NMR) as a powerful technique for the assay of anti-HIV drug efavirenz in human serum and pharmaceutical formulations

“…Since the sample preparation and pre-concentration are usually a critical part of high put quantitative bioanalysis, various methods such as liquid-liquid extraction (Ramachandran et al, 2006;Lakshmi et al, 2007;Langmann et al, 2001), solid phase extraction (Aymard et al, 2000;Rezk et al, 2004;Sarasa-Nacenta et al, 2001;Simon et al;2001) and a protein precipitation method followed by a dilution step with distilled water (Kappelhoff et al, 2003) have been used to extract efavirenz from plasma. Nuclear magnetic resonance (NMR) has gained widespread acceptance over recent years as a most versatile tool for industrial drug research (Aman et al, 2005;Gil Garcya et al, 2006;Ellis et al, 2000;Lenz et al, 2002;Shamsipur et al, 2002, a, b;Talebpour et al, 2003aTalebpour et al, , b, 2004aWenyi et al, 2006). Since fluorine atoms are not naturally present in biological fluids, the 19 F NMR spectra of these matrices containing desirable Fsubstituted analytes and their metabolites are generally highly simplified, in comparison with the corresponding 1 H NMR spectra.…”

“…As a basis for quantitative determination of fluorinated species, 19 F NMR offers several potential advantages compared to chromatography; these include nuclear spin of 1/2 , relatively narrow lines, 100% natural abundance, high sensitivity for fluorine-19 nucleus (83% that of proton) and correct sensitivity, large chemical shift range (300 ppm), which minimizes signal overlap used as a powerful, universal and fast-screening technique to evaluate the quality and quantity of drugs (Hull et al, 1988;Lenz et al, 2002;Shamsipur et al, 2007a, b). An important advantage, specific to 19 F NMR, is that the resonances of fluorine nuclei can be observed without problems of interfering background signals, since the level of endogenous fluorine-containing compounds is very low (Hull et al, 1988).…”