Optimization of a simple method for the chiral separation of methamphetamine and related compounds in clandestine tablets and urine samples by β-cyclodextrine modified capillary electrophoresis: a complementary method to GC–MS

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Abstract

The chiral separation of (±)-methamphetamine, (±)-methcathinone, (±)-ephedrine and (±)-pseudoephedrine by means of β-cyclodextrine modified capillary electrophoresis is described. The distribution of enantiomers in clandestine tablets and urine samples were identified. Several electrophoretic parameters such as the concentration of β-cyclodextrin, temperature, the applied voltage and the amount of organic solvent required for successful separation were optimized. The method, as described herein, represents a good complementary method to GC–MS for use in forensic and clinical analysis.

Introduction

Methamphetamine and its analogues are strong central nervous system stimulants and are classified as illicit drugs, and are currently a source of serious social problems in many countries. In general, (+)-methamphetamine can be synthesized from (−)-ephedrine or (+)-pseudoephedrine; (−)-methamphetamine can be produced from (+)-ephedrine or (−)-pseudoephedrine (Fig. 1) [1]. Thus, the separation and identification of these enantiomers are a great significance, not only with respect to providing valuable information concerning the clandestine conversion of norephedrine and norpseudoephedrine to amphetamine and ephedrine, and pseudoephedrine to methamphetamine [2], [3], [4] but also would be useful in clinical analysis. It is especially worthy noting that (−)-methamphetamine can also be extracted from a Vicks Inhaler [5] and that (−)-methamphetamine if used in certain prescription drugs [6]. To avoid errors in judgment, an enantiomeric analysis would be highly desirable. Currently, separation methods used for the separation of enantiomers either are chromatographic, such as gas chromatography (GC) [7], high performance liquid chromatography (HPLC) [8], [9], [10], or an elctrophoretic method such as capillary electrophoresis (CE) [11], [12], [13], [14]. LeBelle et al. has also reported the chiral identification of (±)-ephedrine compounds by both GC after derivatization with (R)(+)-α-methoxy-α-(trifluoromethyl)phenylacetic acid (MTPA) and by nuclear magnetic resonance (NMR) using a chiral solvating agent ((R)(+)-1,1’-bi-2-naphthol) [7]. Derivatization of (±)-ephedrine, (±)-pseudoephedrine and related substances with 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl isothiocyanate (GITC) permitted enantiomeric separations by micellar electrokinetic chromatography (MEKC), as reported in the literature [11]. The determination of (±)-ephedrine compounds in nutritional supplements has also been investigated by cyclodextrin-modified capillary electrophoresis, using hydroxypropyl-β-cyclodextrin (HP-β-CD) [11].

Thus far, GC–MS still remains the officially prescribed method. However, for the chiral separation of methamphetamine related compounds it is necessary to derivatize the analytes prior to their injection into the GC system. All of these procedures are time consuming. Furthermore, hundreds of samples are frequently involved in routine testing and, as a result, a simple and rapid method which is also reliable and complementary to GC–MS for use in forensic analysis would be highly desirable.

In this study, the optimum conditions for the separation and determination of (±)-methamphetamine, (±)-methcathinone, (±)-ephedrine and (±)-pseudoephedrine using native β-CD in conjunction with CE is described. Several electrophoretic parameters, such as concentration of β-CD and the amount of organic solvent needed for the separation were optimized. The distribution of each single enantiomer in clandestine tablets and suspect urine samples were identified.

Section snippets

Reagents

(±)-Methamphetamine, (±)-methcathinone, (±)-ephedrine and (±)-pseudoephedrine obtained from Radian International (Austin, TX, USA). β-Cyclodextrin and acetonitrile were purchased from Sigma (St. Louis, MO, USA) and Acros (Belgium), respectively. All of the tablets and urine samples were generously donated by Command of the Army Force of Military Police, Forensic Science Center, Taiwan.

CE apparatus

A capillary electrophoresis system (Hewlett-Packard 3DCE system, Germany) equipped with a photodiode array

Identification of standards

Fig. 1 shows the molecular structures of (±)-methamphetamine, (±)-methcathinone, (±)-ephedrine and (±)-pseudoephedrine. These compounds possess a chiral center: the (+) and (−) forms have different pharmacological activities [15], [16], [17].

In the case of CE separation, β-CD is most commonly used chiral additive. However, less soluble (1.8 g per 100 ml at 250 °C) in water [18], highly sulfated cyclodextrins have been developed by Beckman (http://www.beckmancoulter.com/) to improve solubility.

Conclusions

We demonstrated here that a β-CD modified CE method can be successfully used for the separation and identification of: (±)-methamphetamine, (±)-methcathinone, (±)-ephedrine and (±)-pseudoephedrine, (±)-amphetamine in clandestine tablets and urine samples of suspects. The optimum CE conditions for the analysis of these analytes was achieved using a mixture of water–acetonitrile solution (95:5 (v/v)) containing phosphate (150 mM), β-CD (17.5 mM) at 15–30 °C; applied voltage, 20–25 kV. This method has

Acknowledgements

This work was supported by a grant from the National Science Council of Taiwan under Contract no. 90-2113-M-003-020. Permission was obtained from Pharmaceutical Affairs, Department of Health, Taiwan (License number: ARR089000035). The authors wish to thank the Forensic Science Center (Taiwan Command of the Army Force of Military Police) for generously donating the urine samples and amphetamine standards.

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