Application of sweat patch screening for 16 drugs and metabolites using a fast and highly selective LC-MS/MS method.
BACKGROUND
To facilitate the monitoring of drug abuse by patients, a method was developed and validated for fast and highly selective screening for amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylphenidate, cocaine, benzoylecgonine, morphine, codeine, heroin, 6-monoacteylmorphine, methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, nicotine, and cotinine in PharmCheck sweat patches. The analysis of sweat patches would provide a noninvasive alternative matrix to urine or blood samples.


METHODS
The sweat patches were extracted during vigorous shaking for 10 minutes with 1.5 mL of 20 mmol/L ammonium formate, pH 7, and methanol (50%:50% vol/vol). The extracts were cleaned up by filtering through Whatman mini-Uniprep syringeless filter vials before injection. The method uses a single injection to detect and confirm all 16 drugs and metabolites within 9.6 minutes.


RESULTS
The validated substances have a linear range of 3.0-300 nanograms per patch, except for nicotine which has a linear range of 30-3750 nanograms per patch. Stabilities of all substances in worn sweat patches were validated at room temperature for 7 days and as a processed sample in the autosampler at 10°C for 5 days. Only heroin was unstable, with high individual variability and reported bias and coefficient of variation of, respectively, -30.6% and 22.1% in worn sweat patches at room temperature. The monitoring of ion ratios was added to the validation criteria. This resulted in analytical cutoff concentrations of 3.0 and 60 nanograms per patch for nicotine with validated qualifier/quantifier ratios. All analytical cutoff concentrations were lower than the cutoff concentrations proposed by the Substance Abuse and Mental Health Services Administration.


CONCLUSIONS
The method uses validated cutoff concentrations, qualifier/quantifier ratios, and a simple extraction without extensive sample treatment for the analysis of 16 drugs and metabolites with a runtime of 9.6 minutes. This method was successfully applied for the analysis of 96 worn sweat patches to monitor patients for drug abuse. The results provided the physician or health-care professional with information about drug abuse and could be used to improve patient care with patient-specific therapy.
*Laboratory for Clinical and Forensic Toxicology and Drugs Analysis, Department of Hospital and Clinical Pharmacy, University of Groningen, University Medical Center Groningen, The Netherlands; †SumID-Project, Zorgontwikkeling, Tactus Addiction Medicine, Deventer, The Netherlands; and ‡ACSW-Nijmegen Institute for Scientist-Practitioners in Addiction, Radboud University, Nijmegen, The Netherlands.
Remco A
RA
Koster
Jan-Willem C
JW
Alffenaar
Ben
B
Greijdanus
Joanneke E L
JE
VanDerNagel
Donald R A
DR
Uges
D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D013287:Illicit Drugs / Q000032:analysis; D012680:Sensitivity and Specificity; D015813:Substance Abuse Detection / Q000379:methods*; D019966:Substance-Related Disorders / Q000175:diagnosis; D013542:Sweat / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
D013287:Illicit Drugs