the application of microextraction for the the application of microextraction for the determination

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  • Literature Thesis

    THE APPLICATION OF MICROEXTRACTION

    FOR DETERMINATION OF DRUGS

    IN BIOLOGICAL SAMPLES

    Febri Annuryanti

    Supervisor: Dr. Henk Lingeman

    Master in Chemistry – Analytical Sciences

    University of Amsterdam

  • MSc Chemistry

    Analytical Sciences

    Literature Thesis

    The Application of Microextraction for Determination

    of Drugs in Biological Samples

    by

    Febri Annuryanti

    April 2013

    Supervisor:

    Dr. Henk Lingeman

    Daily Supervisor:

    Dr. Wim Th. Kok

  • i Febri Annuryanti [10145222]

    Table of contents :

    Table of contents i

    Abbreviations ii I. Introduction 1

    II. Liquid-phase Microextraction (LPME) 3

    2.1 Principle of LPME 3

    2.2 Classification of LPME 3

    2.2.1 Single-drop microextraction (SDME) 3

    2.2.2 Hollow fiber microextraction (HF-LPME) 6

    2.2.3 Carrier-mediated HF-LPME 8

    2.2.4 Dispersive liquid-liquid membrane (DLLME) 9

    2.3 Recovery and enrichment factor 11

    2.3.1 In SDME, HF-LPME, and carrier mediated HF-LPME 11

    2.3.2 In DLLME 12

    2.4 Influence factors on the LPME efficiency 13

    2.4.1 Organic solvent 13

    2.4.2 Volume of donor and acceptor solution 13

    2.4.3 Extraction time 14

    2.4.4 pH adjustment 14

    2.4.5 Agitation of the sample 15

    2.4.6 The addition of salt 15

    III. Solid-phase Microextraction (SPME) 16

    3.1 Principle of SPME 16

    3.2 Classification of SPME 18

    3.2.1 Fiber SPME 18

    3.2.2 In-tube SPME 19

    3.3 Influence factors on the SPME efficiency 20

    3.3.1 Agitation method 20 3.3.2 Sample pH 20 3.3.3 Ionic strength 21 3.3.4 Sample temperature 21 3.3.5 Sample derivatization 22

    IV. Discussion 23 4.1 Recent applications of LPME for determination of drugs in biological

    samples 4.2 Recent applications of SPME for determination of drugs in biological

    samples

    23

    37

    V. Conclusion 43 VI. References 45

  • ii Febri Annuryanti [10145222]

    Abbreviations

    LLE = Liquid-liquid extraction SPE = Solid-phase extraction

    HPLC = High-performance Liquid Chromatography GC = Gas Chromatography CE = Capillary Electrophoresis

    SPME = Solid-phase microextraction LPME = Liquid-liquid microextraction

    DI = Direct immersion HS = Head space

    HS-SDME = Head space single-drop microextraction SDME = Single-drop microextraction

    CF-SDME = Continous flow single-drop microextraction DLLME = Dispersive liquid-liquid microextraction PDMS = Polydimethylsiloxane

    PA = Polyacrylate PDMS-DVB = Polydimethylsiloxane-divinylbenzene

    CW-TPR = Carbowax-templated resin LC-MS = Liquid chromatography-Mass spectrometry GC-FID = Gas-Chromatography-Flame Ionization Detector

    NPD = Nitrogen-phosphorus detector LOD = Limit of detection LOQ = Limit of quantification I.S. = Internal standard TSD = Thermionic specific detector

  • THE APPLICATION OF MICROEXTRACTION FOR THE DETERMINATION OF DRUGS IN BIOLOGICAL SAMPLES

    1 Febri Annuryanti [10145222]

    Introduction

    Analysis of drugs in biological samples is becoming increasingly important due

    to the need to understand more about the therapeutic and the toxic effects of drugs

    [1,2]. Many advantages are obtained by knowing the drug levels in body fluids such as in

    plasma, serum, and urine [1-3]. The data of drug levels can be used to optimize

    pharmacotherapy and give the basis for studies on patient compliance [1-3], to perform

    routine drug monitoring [1,2], to compare the pharmacokinetics study for release of

    new drugs [6], to reveal the influence of co-medication and to monitor the organ

    function [2,3]. Furthermore, the screening of drug abuse in body fluids may be used to

    identify potential users of illegal drugs and to control drugs addicts following

    withdrawal therapy [1,2].

    Although there is an advance development of analytical instrumentation for the

    determination of analytes in biological fluids, most of the instruments cannot handle

    the sample matrices directly because of sample complexity [1-2,4]. Biological samples

    may contain acids, bases, proteins, salts and other organic compounds that may have

    chemical properties similar to the analyte of interest [3,5,7]. Therefore, sample

    preparation becomes a crucial part of analysis in order to extract, isolate, and

    concentrate the analytes [1-3,7-8]. In addition to complex matrices, limited sample

    volumes and low analyte concentrations have to be considered during sample

    preparation [2,7]. In order to get an efficient sample pre-treatment, it is important to

    minimize sample loss so the analytes can be recovered in good yield [1,2], coexisting

    components can be removed efficiently [1,2], problems do not occur in chromatography

    system, the analysis cost is low and the procedure can be performed quickly [1,2].

    Conventionally, sample preparation is carried out by liquid-liquid extraction

    (LLE) or by solid-phase extraction (SPE) and the final analysis is accomplished by High-

    performance Liquid Chromatography (HPLC), Gas Chromatography (GC) or Capillary

    Electrophoresis (CE) [3,5-6,9-10]. However, both of LLE and SPE have various drawbacks

  • THE APPLICATION OF MICROEXTRACTION FOR THE DETERMINATION OF DRUGS IN BIOLOGICAL SAMPLES

    2 Febri Annuryanti [10145222]

    such as requires large amounts of organic solvents that are toxic and expensive [8,11],

    time-consuming [8], result in hazardous waste [11], tedious [8], laborious, and difficult to

    automate [4].

    An ideal sample preparation technique should be easy to use, inexpensive, fast

    and compatible with a range of analytical instruments [2,4]. To overcome or reduce the

    drawbacks of LLE and SPE, miniaturizations have been reported on alternative sample

    preparation methods for drug analysis, namely solid-phase micro extraction (SPME)

    and liquid-phase micro extraction (LPME) [2,10,12].

    This article presents the main principle of SPME and LPME, factors that

    affecting SPME and LPME, their application on determination of drugs in biological

    fluids, and further prospect of LPME for drug analysis in biological samples.

  • THE APPLICATION OF MICROEXTRACTION FOR THE DETERMINATION OF DRUGS IN BIOLOGICAL SAMPLES

    3 Febri Annuryanti [10145222]

    Liquid-Phase Microextraction (LPME)

    2.1 Principle of LPME

    LPME is a new sample-preparation technique for the extraction of analytes.

    Basically, LPME is performed between a small amount of water immiscible solvent

    (known as acceptor phase) and an aqueous phase containing the analyte of interest

    (donor phase) [1,4,13,14]. The volume of acceptor phase is usually in the microliter or

    submicroliter region, while the donor phase between 0.5-4.0 mL for biological samples

    [8,15,16]. Hence, high analyte enrichments are obtained because of the high sample

    volume-to-acceptor phase volume ratio [8]. LPME procedures can be divided into static

    and dynamic mode. In static mode, the extractant is suspended in a large volume of

    sample phase and the extraction of the analytes is passively carried out. In dynamic

    mode, extraction occurs by withdrawing aqueous sample into the extraction unit

    (usually a micro syringe) that already containing solvent. The aquase phase is then

    pushed out of the syringe and this procedure is repeated several times (typically 20

    times) so a higher enrichment factors is obtained [4,17,18]. As a sample preparation,

    LPME has many advantages. It is rapid, effective, minimize exposure to toxic organic

    solvents and inexpensive [1,3]. The LPME concept is also compatible for analysis of drugs

    using HPLC, GC or CE [19].

    2.2 Classification of LPME

    In general, LPME can be divided into single-drop microextraction (SDME), hollow-

    fiber microextraction, and dispersive liquid-liquid microextraction (DLLME) [4].

    2.2.1 Single-drop microextraction (SDME)

    SDME is the simplest form of LPME. It is based on the extraction of analytes

    into a small drop of organic solvent that is held at the tip of a micro syringe needle [20].

    In a two-phase system, the organic solvent was placed into the aqueous sample and

    the analytes are extracted into the organic solvent based on passive diffusion. In a

    three-phase system, analytes are extracted from an aqueous sample into the organic

  • THE APPLICATION OF MICROEXTRACTION FOR THE DETERMINATION OF DRUGS IN BIOLOGICAL SAMPLES

    4 Febri Annuryanti [10145222]

    phase. Then, analytes are “back extracted” into a separate aqueous phase [1]. After

    extraction, the organic phase is retracted into the needle and the syringe is transferred

    for further analysis [4]. In practice, there are three main approaches to perform SDME,

    direct immersion (DI)-SDME, head space (HS)-SDME, and continuous flow (CF)-SDME

    [6,20].

    DI-SDME is a static mode of LPME. It can be done in a two-phase or a three-

    phase system (Fig. 1). It is b

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