145
ISSN 1061-9348, Journal of Analytical Chemistry, 2018, Vol. 73, No. 2, pp. 145–151. © Pleiades Publishing, Ltd., 2018.
Extraction and Determination of Two Antidepressant Drugs in Human
Plasma by Dispersive Liquid–Liquid Microextraction‒HPLC
1
Gholamreza Vaghar-Lahijani
a
, Mohammad Saber-Tehrani
a,
*,
Parviz Aberoomand-Azar
a
, and Mojtaba Soleimani
b
a
Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran
b
Department of Chemistry, Lahijan Branch, Islamic Azad University, Lahijan, Iran
*e-mail: Drmsabertehrani@yahoo.com
Received June 19, 2016; in final form, April 6, 2017
Abstract⎯In this study, an effective method of ultrasound-assisted ionic liquid based dispersive liquid–liq-
uid microextraction (UA−IL−DLLME) coupled with HPLC was applied for extraction and determination of
two antidepressant drugs: venlafaxine hydrochloride and amitriptyline hydrochloride from human plasma
samples. Three ionic liquids were studied: 1-butyl-3-methyl imidazolium hexafluorophosphate, 1-hexyl-3-
methyl imidazolium hexa-fluoro-phosphate, and 1-octyl-3-methyl imidazolium hexafluorophosphate
[C8MIM][PF6]. Various factors affect the stages and efficiency of extraction, some of which are pH of sam-
ple solution, type and volume of ionic liquid, the time of ultrasonication, centrifuging time and rate, and the
ionic strength of solution. In this research, optimum conditions were obtained as 55 μL of [C8MIM][PF6]
selected as ionic liquid, pH 11, 2% NaCl, 4 min ultrasonication and 5 min centrifuging at 3500 rpm. Under
the optimized conditions, the linearity was obtained in the range of 0.2 to 250 μg/L. The limits of detection
were 0.5 μg/L for venlafaxine and 0.8 μg/L for amitriptyline. Pre-concentration factors were 1.3 × 10
3
for
venlafaxine and 1.2 × 10
3
for amitriptyline. The UA−IL−DLLME method coupled with HPLC was success-
fully used for the determination of venlafaxine and amitriptyline spiked into the real samples of human
plasma.
Keywords: ultrasound-assisted ionic liquid based dispersive liquid–liquid microextraction (UA−IL−
DLLME), HPLC, antidepressant drugs, human plasma sample, amitriptyline, venlafaxine
DOI: 10.1134/S1061934818020144
Antidepressant drugs are used for treatment of
depression. These drugs were introduced the market
in 1950s. In general, antidepressant drugs are divided
into four classes: tricyclic antidepressants (TCA),
selective serotonin reuptake inhibitors (SSRI), mono-
amine oxidase inhibitors and other [1, 2]. For exam-
ple, venlafaxine hydrochloride is a SSRI antidepres-
sant with pK
a
= 10.09, while amitriptyline hydrochlo-
ride is a TCA antidepressant with pK
a
= 9.4 [3]. Both
mentioned drugs are basic compounds.
Different methods have been suggested for separa-
tion, extraction and pre-concentration of drugs in bio-
logical samples. Some methods such as liquid–liquid
extraction [4, 5], solid phase extraction [6, 7], liquid
phase microextraction and dispersive liquid–liquid
microextraction [8–13] have been used widely.
Recently, the use of controlled temperature ultra-
sound along with ionic liquid based dispersive liquid-
liquid microextraction method has been developed
[14, 15]. In the present study, we aimed to measure two
antidepressant drugs, amitriptyline and venlafaxine,
in human plasma samples by the use of HPLC which
needs pre-concentration of analytes. For this purpose,
UA−IL−DLLME method was applied and the param-
eters that could affect extraction efficiency and mea-
surement conditions were investigated.
EXPERIMENTAL
Chemicals and Reagents
Standard amitriptyline hydrochloride and venla-
faxine hydrochloride were prepared from Darou
Pakhsh Co. (Tehran, Iran) and Sobhan Darou Co.
(Guilan, Iran). 1-Butyl-3-methyl- imidazolium hexa-
fluoro-phosphate [C4MIM][PF6], 1-hexyl-3-
methyl-imidazolium hexa-fluoro-phosphate
[C6MIM][PF6] and 1-octyl-3-methyl- imidazolium
hexa-fluoro-phosphate as ionic liquids, methanol,
acetonitrile of HPLC grade, sodium hydroxide and
sodium chloride, all with high purity, were procured
from Fluka and Merck. Plasma samples were obtained
from a healthy person.
1
The article is published in the original.
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