Development of new extraction method based on liquid–liquid–liquid extraction followed by dispersive liquid–liquid microextraction for extraction of three tricyclic antidepressants in plasma samples

Abstract

In the present study, a new extraction method based on a three-phase system, liquid-liquid-liquid extraction, followed by dispersive liquid-liquid microextraction has been developed and validated for the extraction and preconcentration of three commonly prescribed tricyclic antidepressant drugs - amitriptyline, imipramine, and clomipramine - in human plasma prior to their analysis by gas chromatography-flame ionization detection. The three phases were an aqueous phase (plasma), acetonitrile and n-hexane. The extraction mechanism was based on the different affinities of components of the biological sample (lipids, fatty acids, pharmaceuticals, inorganic ions, etc.) toward each of the phases. This provided high selectivity toward the analytes since most interferences were transferred into n-hexane. In this procedure, a homogeneous solution of the aqueous phase (plasma) and acetonitrile (water-soluble extraction solvent) was broken by adding sodium sulfate (as a phase separating agent) and the analytes were extracted into the fine droplets of the formed acetonitrile. Next, acetonitrile phase was mixed with 1,2-dibromoethane (as a preconcentration solvent at microliter level) and then the microextraction procedure mentioned above was performed for further enrichment of the analytes. Under the optimum extraction conditions, limits of detection and lower limits of quantification for the analytes were obtained in the ranges of 0.001-0.003 and 0.003-0.010 μg mL , respectively. The obtained extraction recoveries were in the range of 79-98%. Intra- and inter-day precisions were < 7.5%. The validated method was successfully applied for determination of the selected drugs in human plasma samples obtained from the patients who received them.

New Method for the Monitoring of Antidepressants in Oral Fluid Using Dried Spot Sampling

“…One of the steps to take into account in an analytical method is the isolation and concentration of analytes of interest from the biological samples under study; the most used procedures for extracting antidepressants are liquid-liquid extraction (LLE) [6,17], solid-phase extraction (SPE) [6,[18][19][20], and some miniaturized techniques-such as solidphase microextraction (SPME) [6,21,22], microextraction by packed sorbent (MEPS) [6,[23][24][25], and dispersive liquid-liquid microextraction (DLLME) [6,[26][27][28][29][30][31]. There are also several methods involving gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry (MS) [26,[30][31][32][33][34][35][36][37][38] or tandem mass spectrometry (MS/MS) [27,[39][40][41][42][43], ultraviolet (UV) [22,28,[44][45][46][47][48], fluorescence [25], diode array (DAD) or photodiode array (PDA)…”

A Comprehensive Review on Developed Pharmaceutical Analysis Methods by Iranian Analysts in 2018

“…They reported a sodium valproate concentration in the ranges of 9.9 -34.7 µg mL -1 and 0.5-6.7 µg mL -1 for analyzed patient's plasma and urine samples, respectivly. Farajzadeh et al 130 reported a GC-FID method for determination of amitriptyline, imipramine, and clomipramine in plasma samples after extraction by liquid-liquid-liquid extraction (LLLE) (acetonitrile as extraction solvent, n-hexane as clean up and co-extraction solvent and sodium sulfate as phase separating agent) followed by DLLME method by 1,2-dibromoethane as preconcentration solvent.…”

Development of Sodium Sulfate Induced Water Based Dispersive Liquid–Liquid Microextraction for the Extraction of Four Tricyclic Antidepressants in Urine Samples Prior to Their Determination by Gas Chromatography–Mass Spectrometry

“…Also, DLLME was used for determination of TCAs in biological samples in the previously published papers. 27,[29][30][31][32][33][34][35][36][37][38][39][40][41] Even though, these method removes the main deficiencies of the customary extraction approaches but it also requires toxic organic solvents like chlorinated or aromatic solvents howbeit much less compared to the previous methods. The aim of the present work was to suggest a new and green version of DLLME without using common disperser and extraction solvents.…”

“…In the first part, Na 2 SO 4 was added into deionized water (disperser) to prevent the reduction of ionic strength of aqueous sample after injection of the mixture of deionized water and isopropanol into it. To optimize this parameter, various concentrations of Na 2 SO 4 (15-40%, w/v) were added into deionized water, while the other parameters, except isopropanol volume (160, 152, 144, 134, 126, and 120 μL of isopropanol for15,20,25,30,35, and 40 % w/v, of Na 2 SO 4 , respectively) were kept constant during the microextraction procedure.…”