LC–MS/MS method for quantification of baclofen in hair: A useful tool to assess compliance in alcohol dependent patients?

To evaluate adherence to treatment, we developed and validated a novel liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for baclofen quantification in hair.Twenty mg was washed twice with dichloromethane, incubated in phosphate buffer (pH 5) for 10 minutes at 95°C, then extracted by...

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Bibliographic Details
Published in:	Drug testing and analysis Vol. 10; no. 4; pp. 694 - 700
Main Authors:	Larabi, I.A., Fabresse, N., Knapp, A., Forcet, M., Baud, F.J., Lorin de la Grandmaison, G., Alvarez, J.C.
Format:	Journal Article
Language:	English
Published:	England Wiley Subscription Services, Inc 01-04-2018
Subjects:	Alcohol alcohol dependence Alcoholism - blood Alcoholism - diagnosis Alcoholism - drug therapy baclofen Baclofen - analysis Baclofen - blood Baclofen - therapeutic use Biomarkers - analysis Biomarkers - blood Chromatography, Liquid - methods Drug Monitoring - methods Drug testing Ethanol - analysis Ethanol - blood ethyl glucuronide Female GABA-B Receptor Agonists - analysis GABA-B Receptor Agonists - blood GABA-B Receptor Agonists - therapeutic use Glucuronates - analysis Glucuronates - blood hair Hair - chemistry Humans Limit of Detection Male mass spectrometry Middle Aged Patient compliance Patients Tandem Mass Spectrometry - methods mass spectrometry hair ethyl glucuronide alcohol dependence baclofen
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Summary:	To evaluate adherence to treatment, we developed and validated a novel liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for baclofen quantification in hair.Twenty mg was washed twice with dichloromethane, incubated in phosphate buffer (pH 5) for 10 minutes at 95°C, then extracted by liquid‐liquid extraction in alkaline condition. Baclofen‐d4 was used as the internal standard. This method was applied to assess compliance in4 treated alcohol‐dependent patients (3 dead and one living). Blood quantification of baclofen and ethanol were performed in the 4 cases. Hair ethylglucuronide (ethanol metabolite, EtG) measurement (2x3 cm) was associated in 1 patient. Baclofen quantification in hair was validated over the range 10–5000 pg/mg. The accuracy was within 96.0%–110.9% and the precision was less than 9.3%. Baclofen segmental (3x2cm) hair concentrations found in the living patient were 4420, 4260, and 4380 pg/mg, reflecting a regular exposure over the last 6 months and suggesting patient compliance. However, the high EtG level found in this patient in the analyzed segments (225 pg/mg and 215 pg/mg) showed excessive alcohol consumption during the same period, suggesting therapeutic failure. In the 3 deceased patients, the non‐segmental analysis of hair showed baclofen concentrations of 15, 545, and 2475 pg/mg. The low concentrations in the 2 first cases are compatible either with a poor compliance or to a beginning of a treatment. This is the first measurement of baclofen in hair of alcohol dependent patients. It could be used as a monitoring biomarker to assess patient's compliance. The measurement of baclofen in hair could allow to determine the compliance of an alcohol dependent patient to its treatment. Coupled to hair ethylglucuronide determination, these biomarkers could be used both to assess patient's compliance and therapeutic failure in compliant patients.
ISSN:	1942-7603 1942-7611
DOI:	10.1002/dta.2308