A sensitive method for the simultaneous determination in biological fluids of imipramine and desipramine or clomipramine andN-desmethylclomipramine by gas chromatography mass spectrometry

Abstract

A procedure is described which permits the simultaneous determination of imipramine and desipramine or clomipramine and N-desmethylclomipramine in serum or plasma for concentrations in the range of 1-200 ng ml-1. Detection limits of 0.2 ng ml-1 for imipramine and 0.1 ng ml-1 for desipramine were demonstrated with a signal-to-noise ratio maintained at 2:1 or better. The method relies on the derivatization of the secondary amines with heptafluorobutyric anhydride and is based on the combined use of gas chromatography, electron impact mass spectrometry and computerized data handling. The assaying procedure is specific, accurate and precise. It is suitable for routine analyses and has sufficient sensitivity to permit monitoring the drug and metabolite levels in human plasma or serum resulting from a single therapeutic dose.

An Experimental and Theoretical Study of Laser Postionization of Femtosecond-Laser-Desorbed Drug Molecules

“…The difference in calculated charge density on the terminal nitrogen (at the end of the alkyl chain) shown for imipramine in Figure appears to have initiated an α bond cleavage that leads to the formation of the m / z 236 fragment. The m / z 58 peak associated with the dimethylformimine fragment is also relatively intense in both spectra and results from cleavage on the carbon bond β to the dimethylamine. − However, while the counterpart ion to m / z 58 is observed in the EI mass spectrum at m / z 222, the latter is absent from the fs-LDPI mass spectrum, perhaps because of the overall higher energy available in EI-MS. The m / z 86 and 194 ions observed in both the fs-LDPI and EI mass spectra result from cleavage of the bond between the ring nitrogen and the first carbon of the side chain.…”

Development and Validation of a Stability Indicating RP-UPLC Method for Analysis of Imipramine Hydrochloride in Pharmaceuticals

“…Several analytical methods have been reported for the determination of IMH in biological fluids and/or pharmaceutical formulations. These include chromatographic techniques like HPLC [3][4][5][6][7][8][9], TLC [10], GC [11][12][13][14], LC with direct injection and electrochemical detection [15], adsorptive stripping voltammetry [16], chemometric methods [17], flow-injection extraction spectrophotometry [18], derivative spectrophotometry [19,20], and visible spectrophotometry [20][21][22][23][24].…”

“…Many of the reported methods for the determination of imipramine suffer from one or the other disadvantages like time consuming and require expensive experimental setup [11][12][13][14], and chemometric methods are less sensitive [17]. Besides, the reported spectrophotometric methods are less sensitive [18][19][20][21][22][23][24] and require extraction procedures [23] and costly chromogenic reagent [24] (Table 1).…”

“…To our present knowledge, no validated stability indicating UPLC assay method for the determination of IMH in pharmaceutical formulation was available in the literature. Though the numbers of liquid [3][4][5][6][7][8][9], thin layer [10], gas chromatographic methods [11][12][13][14], and LC with direct injection and electrochemical detection [15] earlier for IMH, no attempt has been made to apply this new type of ultra performance liquid chromatography for its determination in pharmaceuticals.…”