High-Performance Liquid Chromatographic Method with Diode Array Detection for Identification and Quantification of the Eight New Antidepressants and Five of Their Active Metabolites in Plasma after Overdose

Abstract

A high-performance liquid chromatographic method is described for the determination of selective serotonin reuptake inhibitors (fluvoxamine, paroxetine, sertraline, fluoxetine, citalopram, mirtazapine), serotonin norepinephrine reuptake inhibitors (milnacipram, venlafaxine), a noradrenergic and specific serotoninergic antidepressant (mirtazapine), and five pharmacologically active metabolites (desmethylcitalopram, didesmethylcitalopram, norfluoxetine, O-desmethylvenlafaxine, desmethylmirtazapine). After a double-step liquid-liquid extraction, compounds are separated on a Symmetry C8 column eluted with a gradient of acetonitrile-phosphate buffer 10 mM pH 3.8 and detected at 230 nm and 290 nm. Calibration curves were linear in the range 25 to 500 ng/mL (100-2000 ng/mL for venlafaxine and its metabolite). The limit of quantification was 25 ng/mL (100 ng/mL for venlafaxine and its metabolite). For all quality controls good accuracy was achieved (93% to 99.5%) with intraday and interday variation coefficients less than 12%. This method allows simple and rapid (run time 18 min) identification and quantification of the eight new antidepressants and five of their active metabolites. This method can be used for toxicologic purpose.

Enantioselective analysis of fluoxetine and norfluoxetine in plasma samples by protein precipitation and liquid chromatography with fluorescence detection

“…These results demonstrate that the developed method allows for the quantification of antidepressants in the therapeutic interval, although no therapeutic levels have been clearly defined for selective serotonin reuptake inhibitors. 20 The stability of standard solutions of FLX and NFLX, as well as plasma samples, had been confirmed in previous studies. 21,22 According to Kovacevic et al, 21 no significant loss is observed for analysis of plasma samples stored in methanol for 18 months at − 20 ºC or after a freeze/thaw 9-month cycle after they were analyzed for the first time.…”

Electroanalytical study of the antidepressant sertraline

“…The determination of STR in serum and plasma is generally performed by high performance liquid chromatography (HPLC) coupled with spectrophotometric detectors, ultraviolet/diode array [1][2][3][4][5][6] and fluorimetric [7,8]. The wide spread usage of HPLC methods is justified by the high sensitivity and low limit of detection usually obtained and the possibility of the simultaneous analysis of the drug and its metabolites, which increases its usage even further.…”

Electroanalytical study of fluvoxamine

“…Most FVX analysis is performed by high-perfor-mance liquid chromatography (HPLC) coupled with spectrometric detectors, ultraviolet/diode array [4][5][6][7][8][9][10][11][12][13][14][15][16][17], mass spectrometric [18,19] and fluorimetric [20][21][22], for analysis of pharmaceuticals [8] and human serum or plasma [4][5][6][7][10][11][12][13][14][15][16][17][18][19][20][21][22]. This widespread usage of HPLC methods is justified by the high sensitivity and the low limit of detection usually obtained and the possibility of simultaneous analysis of the drug and its metabolites, which increases its use even further.…”