Solid-phase extraction and analysis of 20 antidepressant drugs in human plasma by LC/MS with SSI method

https://doi.org/10.1016/j.forsciint.2006.03.038Get rights and content

Abstract

A simultaneous determination of 20 antidepressant drugs (imipramine, amitriptyline, desipramine, trimipramine, nortriptyline, clomipramine, amoxapine, lofepramine, dosulepin, maprotiline, mianserin, setiptiline, trazodone, fluvoxamine, paroxetine, milnacipran, sulpiride, tandspirone, methylphenidate and melitracen) in human plasma was developed using LC/MS with sonic spray ionization (SSI) method. These drugs showed good separation and sensitivity by LC–MS using an Inertsil C-8 column with methanol:10 mM ammonium acetate (pH 5.0):acetonitrile (70:20:10) as mobile phase at 0.10 mL/min at 35 °C. Solid-phase extraction of these drugs added to the human plasma was performed with an Oasis® HLB cartridge column. Recovery and limit of detection of these drugs were between 69 and 102% and between 0.03 and 0.63 μg/mL, respectively. The present procedure offers an easier and more convenient screening method for antidepressants, and will be useful for forensic toxicology investigations.

Introduction

Antidepressant drugs are becoming increasingly widely used for the treatment of depression and these drugs are frequently encountered in emergency toxicology screening, drug-abuse testing and forensic medical examinations [1]. Various methods for determination of antidepressant drugs have been reported, including high-performance liquid chromatography (HPLC) [2], [3], gas chromatography (GC) [4], [5], gas chromatography/mass spectrometry (GC–MS) [6] and high-performance liquid chromatography–mass spectrometry (LC–MS)[7]. However, a sensitive LC–MS method for the simultaneous determination of 20 antidepressant drugs (imipramine, amitriptyline, desipramine, trimipramine, nortriptyline, clomipramine, amoxapine, lofepramine, dosulepin, maprotiline, mianserin, setiptiline, trazodone, fluvoxamine, paroxetine, milnacipran, sulpiride, tandspirone, methylphenidate and melitracen) has not been reported. Furthermore, electrospray ionization (ESI), sonic spray ionization (SSI) developed by Hirabayashi et al. [8] is a very soft ionization method.

The present paper describes a sensitive LC–MS with SSI method for simultaneous determination of 20 antidepressant drugs, and a simple procedure for solid-phase column extraction of the drugs from human plasma with an Oasis® HLB cartridge column.

Section snippets

Chemicals

Imipramine, desipramine, clomipramine, maprotiline and methylphenidate were gifts from Novaltis Pharm Japan (Tokyo, Japan). Fluvoxamine and sulpiride were gifts from Astellas (Tokyo, Japan). Amoxapine and melitracen were from Takeda (Tokyo, Japan). Amitriptyline, trimipramine, nortriptyline, lofepramine, dosulepin, mianserin, setiptiline, trazodone, paroxetine, milnacipran and tandospirone were gifts from Banyu (Tokyo, Japan), Shionogi (Osaka, Japan), Dainippon (Osaka, Japan), Daiichi (Tokyo,

Chromatography and mass spectrometry

When methanol:10 mM ammonium acetate:acetonitrile (70:20:10, v/v/v) was used as the mobile phase, the retention times obtained using the Inertsil C-8 column are listed in Table 1. All drugs were well separated under the conditions used, and every peak was detected within 17.8 min (Table 1).

The 20 antidepressant drugs all exhibited a pseudomolecular ion peak except for milnacipran from the mass spectra obtained by the LC–MS with SSI (positive mode) method. Fig. 1 shows the mass chromatograms of 20

Conclusions

A simple, rapid and sensitive analytical method was developed for the simultaneous determination of 20 antidepressant drugs in plasma using LC–MS technique after solid-phase extraction with an Oasis® HLB cartridge column. This simple and sensitive procedure is suitable from use in forensic toxicology investigations.

Acknowledgment

This work was supported in part by a Grant-in-Aid for Scientific Research (No. 16590545) from Japanese Ministry of Education.

Cited by (129)

  • Determination of 13 antidepressants in blood by UPLC-MS/MS with supported liquid extraction pretreatment

    2021, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
  • Optimization of QuEChERS extraction for detection and quantification of 20 antidepressants in postmortem blood samples by LC-MS/MS

    2021, Forensic Science International
    Citation Excerpt :

    This technique presents some advantages, such as: sensitivity, selectivity, short analysis time and the relatively high throughput that allows the determination of multiple groups of compounds with a single method [16]. Thus, the LC–MS/MS is considered to be useful and effective for the analysis, identification, and quantification of a broad range of drugs, including antidepressants [3,5,17–20]. The aim of the present study was to optimize a QuEChERS extraction from DOE for the determination and quantification of 20 antidepressants in postmortem blood samples using LC–MS/MS analysis.

  • Drug analyses in human plasma by chromatography

    2020, Handbook of Analytical Separations
    Citation Excerpt :

    A few of the HPLC systems have been utilized for the investigation of antidepressant. Juan et al. [109] separated fluoxetine, citalopram, paroxetine, venlafaxine on a MACHEREY-NAGEL C-18 (4.6 mm × 250 mm, 5 μm, Germany) column with a column temperature of 40°C. The mobile phase was water (formic acid: 0.6%, NH4Ac: 30 mmol/L)–acetonitrile (35:65) and was filtered using 0.45 μm filters in a Millipore solvent filtration apparatus and was never recirculated.

View all citing articles on Scopus
View full text