Incorporation of Zolpidem into Hair and Its Distribution after a Single Administration

Drug Metab Dispos. 2017 Mar;45(3):286-293. doi: 10.1124/dmd.116.074211. Epub 2016 Dec 14.


To obtain fundamental information on the drug incorporation into hair, time-course changes in drug distribution along single-strand hair were observed after a single oral administration of zolpidem (ZP), one of the most frequently used hypnotic agents. Quantitative sectional hair analyses of 1-mm segments were performed for each single-strand hair using a validated LC-MS/MS procedure. ZP was detected in all specimens plucked at 10 and 24 hours after a single dose, and the distribution ranged over the whole hair root (4-5 mm in length). A significantly high concentration of ZP was detected in the hair bulb region, whereas much lower concentrations were widely observed in the upper part of the hair root of those samples; this suggested that the incorporation of ZP occurred in two regions, mainly in the hair bulb and to a lesser extent in the upper dermis zone. The ZP-positive area formed lengths of up to 10-12 mm after a single administration, indicating that its incorporation from the hair bulb would continue for about 2 weeks. Time-course changes in the ZP concentration in the hair root additionally revealed that only a small portion of ZP that initially concentrated in the bulb was successively incorporated into the hair matrix and moved toward the keratinized region as hair grew. These findings should be taken into account upon discussing individual drug-use history based on hair analysis. The matrix-assisted laser desorption/ionization mass spectrometry imaging of ZP in the same kinds of hair specimens was also successfully achieved.

MeSH terms

  • Adult
  • Biological Transport
  • Chromatography, Liquid
  • Drug Monitoring / methods*
  • Female
  • Hair / chemistry*
  • Healthy Volunteers
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / pharmacokinetics*
  • Limit of Detection
  • Male
  • Pyridines / administration & dosage
  • Pyridines / pharmacokinetics*
  • Reproducibility of Results
  • Substance Abuse Detection / methods*
  • Tandem Mass Spectrometry
  • Time Factors
  • Zolpidem


  • Hypnotics and Sedatives
  • Pyridines
  • Zolpidem