Quantitative ¹H NMR spectroscopic determination of the E/Z isomer ratio of the antidepressant drug fluvoxamine for use in pharmaceutical analysis

Abstract

High-resolution NMR spectroscopy is a powerful tool in the elucidation of a structure with respect to constitution, configuration and conformation. In recent years, NMR has been increasingly used in quantitative analysis. In this study, we show the ability of 1 H NMR to determine the isomeric composition of the antidepressant drug fluvoxamine. The activity of fluvoxamine resides on the E-isomer, and the current British Pharmacopoeia limits the content of the Z-isomer to 0.5%. The NMR method described here is able to determine the content of the Z-isomer down to the 0.2% level on a total amount of 15 mg of the substance.

Quantitative 1H NMR: Development and Potential of a Method for Natural Products Analysis

“…There is a tendency in the literature to propose internal reference standards with simple 1 H NMR spectra, preferably singlets. The most widely used is maleic acid, which was the reference compound of choice in a number of quantitative qHNMR studies involving catecholamines, 78 muscle relaxants, 79 and antidepressants, 80 as well as in the semiquantitative analyses of herbal drug preparations such as kava-kava 81 and in mixtures of methamphetamine and ephedrine in substances of abuse. 82 The publications by Turczan and co-workers [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] are a valuable source of qHNMR reference standards and include tert-butyl alcohol, 1,4-dinitrobenzene, hexamethylcyclotrisiloxane, methenamine, biphenyl, benzyl benzoate, and again maleic acid.…”

Simultaneous determination of fluvoxamine isomers and quetiapine in human plasma by means of high-performance liquid chromatography

“…In fact, some papers determine the active isomer of FLV alone [9,10] or together with other antidepressants [11,12] by HPLC with UV detection [9,[11][12][13][14]18], gas chromatography [16][17][18] or HPLC with fluorimetric detection after derivatisation [10,15]. Some papers analyse both isomers of FLV, but not in biological fluids, only in solution [19] or in formulations [20]. Only a few papers regard the determination of quetiapine in biological fluids, including HPLC with UV detection [21][22][23][24], HPLC-mass spectrometry [25,26] and gas chromatography-mass spectrometry [21].…”

Electroanalytical study of fluvoxamine

“…The main disad-vantages of HPLC are the relatively long analysis times and high acquisition and maintenance costs. Several other methods, based on electrophoresis [23,24], micellar electrokinetic capillary chromatography [25], isotachophoresis [26], gas chromatography [27][28][29][30], ultraviolet-visible [31][32][33][34][35][36], infrared [31], and nuclear magnetic resonance [31,37] spectrometry, have also --1 Fig. 1 Chemical structure of FVX been described, mainly for determination of FVX in pharmaceutical products.…”