RAPID COMMUNICATIONS IN MASS SPECTROMETRY Rapid Commun. Mass Spectrom. 2003; 17: 472–478 Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/rcm.945 Application of tandem mass spectrometry combined with gas chromatography and headspace solid-phase dynamic extraction for the determination of drugs of abuse in hair samples Dirk W. Lachenmeier*, Lars Kroener, Frank Musshoff and Burkhard Madea Institute of Legal Medicine, University of Bonn, Stiftsplatz 12, 53111 Bonn, Germany Received 25 October 2002; Revised 20 December 2002; Accepted 20 December 2002 A new method combination, headspace solid-phase dynamic extraction coupled with gas chroma- tography/tandem mass spectrometry (HS-SPDE/GC/MS/MS), is introduced to determine drugs of abuse in hair samples. This highly automated procedure utilizes SPDE for pre-concentration and on-coating derivatization as well as GC and triple quadrupole MS/MS for selective and sensitive detection. All these steps, apart from washing and cutting of the hair samples, are performed with- out manual intervention on a robot-like autosampler. SPDE is a solventless extraction technique related to solid-phase microextraction (SPME). The analytes are absorbed from the sample headspace directly into a hollow needle with an internal coating of polydimethylsiloxane by repeated aspirate/dispense cycles. The HS-SPDE/GC/MS/MS procedure was applied to the analysis of methadone, the trimethylsi- lyl derivatives of cannabinoids and the trifluoroacetyl derivatives of amphetamines and designer drugs. The method was shown to be sensitive with detection limits between 6 and 52 pg/mg hair matrix and precision between 0.4 and 7.8% by the use of an internal standard technique. Linearity was obtained from 0.1–20 ng/mg with coefficients of correlation between 0.995 and 0.999. Compared with conventional methods of hair analysis, HS-SPDE/GC/MS/MS is easier to use, substantially faster, with the degree of sensitivity and reproducibility demanded in clinical and forensic toxicology. The main advantage of the SPDE technique in relation to SPME is the robust- ness of the capillary. Copyright # 2003 John Wiley & Sons, Ltd. Gas chromatography coupled with mass spectrometry (GC/ MS) seems to be the method of choice for analysis of drugs of abuse in hair samples. 1,2 The overwhelming majority of these procedures involves the quadrupole mass spectrometer operating in selected ion monitoring (SIM) mode. However, the analysis of minor organic compounds in complex matrices like hair is difficult because of interferences by matrix components, even when extensive clean-up proce- dures are applied to the sample. One approach to eliminate these interferences is the use of GC coupled to tandem mass spectrometry (MS/MS) using triple quadrupole 3–5 or ion trap mass spectrometers 6 for hair analysis, giving an improved sensitivity and specificity especially preferable for forensic purposes. For a long time this technology was restricted to expensive instruments, and rather used for structural characterization, e.g., of designer drugs 7,8 than for quantification. Recently, the introduction of low-cost benchtop triple quadrupole mass spectrometers has made it possible to adopt these techniques. For this reason the Kodiak 1200 MS/MS system uses a 1808 curved collision cell, which also positions the electron multiplier off-axis from the source for lower background noise. To evaluate this technique the mass spectrometer was operated in multiple reaction moni- toring (MRM) mode rather than in SIM mode. In order to achieve an efficient isolation and pre-concen- tration of drugs from the hair matrix, several methods for sample preparation have been developed, predominantly using liquid–liquid extraction or solid-phase extraction. 1,2 However, these traditional methods are time-consuming, labour intensive, may require large volumes of sample and solvent and require additional instrumentation to automate. Solid-phase microextraction (SPME), developed by Pawlis- zyn and co-workers in 1990, 9 integrates sampling, extraction, concentration and sample introduction in a single procedure, using a small fused-silica fibre that is coated on the surface with an appropriate stationary phase. Because of the advantages of SPME, like simplicity, speed of operation and the reduction in solvent requirements, a large number of applications for SPME-GC/MS have been reported, includ- ing hair analysis for amphetamines and their methylendioxy derivatives, 10–13 cannabinoids, 14,15 as well as methadone. 16,17 While these methods show that SPME is a good alternative, Copyright # 2003 John Wiley & Sons, Ltd. *Correspondence to: Dirk W. Lachenmeier, Institute of Legal Medicine, University of Bonn, Stiftsplatz 12, D-53111 Bonn, Germany. E-mail: lachenmeier@web.de