Degradation of zopiclone during storage of spiked and authentic whole blood and matching dried blood spots

R. Jantos, A. Vermeeren, D. Sabljic, J.G. Ramaekers, G. Skopp

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Scopus)

Abstract

Z-drugs such as zopiclone are increasingly involved in forensic cases. Its degradation occurs in solvents and biological fluids. It is assumed that hydrolysis largely accounts for the breakdown of zopiclone in aqueous media. Therefore, a stability study in blood at different storage conditions (-20, 4, 20, and 40A degrees C) was performed to establish changes of the drug's concentration with time, also including its degradation product 2-amino-5-chloropyridine (ACP). As removal of the aqueous phase may stabilize molecules that are prone to hydrolysis, it was assessed whether the use of dried blood spots (DBS) may be an alternative for storing and analyzing zopiclone and ACP. Spiked and authentic blood samples and corresponding DBS were analyzed using fully validated LC-MS/MS assays. There was agreement between the measurement of zopiclone from either blood or matching DBS in freshly prepared samples. Results showed that zopiclone was unstable in blood at all storage temperatures except at -20A degrees C. Stability of zopiclone in spiked and authentic blood was increased in DBS compared to matching blood samples stored at the same condition. About 85 % of the initial concentration of zopiclone was still intact in DBS on day 8 at 20A degrees C. ACP was formed from zopiclone in equimolar amounts in both media. Therefore, determination of both zopiclone and ACP may be helpful to estimate the initial concentration in both media. Pre-analytical conditions have a major impact on the recovery of zopiclone from blood. With respect to its known advantages, DBS can be recommended as a valuable alternative for the determination of zopiclone from blood.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalInternational Journal of Legal Medicine
Volume127
Issue number1
DOIs
Publication statusPublished - 1 Jan 2013

Keywords

  • Zopiclone
  • Stability
  • Dried blood spots
  • Whole blood
  • LC-MS/MS
  • BIOANALYTICAL METHOD VALIDATION
  • DRIVING PERFORMANCE
  • STABILITY
  • PLASMA
  • 2-AMINO-5-CHLOROPYRIDINE
  • BENZODIAZEPINES
  • SPECTROMETRY
  • TOXICOLOGY
  • MOLECULES
  • ZALEPLON

Cite this

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title = "Degradation of zopiclone during storage of spiked and authentic whole blood and matching dried blood spots",
abstract = "Z-drugs such as zopiclone are increasingly involved in forensic cases. Its degradation occurs in solvents and biological fluids. It is assumed that hydrolysis largely accounts for the breakdown of zopiclone in aqueous media. Therefore, a stability study in blood at different storage conditions (-20, 4, 20, and 40A degrees C) was performed to establish changes of the drug's concentration with time, also including its degradation product 2-amino-5-chloropyridine (ACP). As removal of the aqueous phase may stabilize molecules that are prone to hydrolysis, it was assessed whether the use of dried blood spots (DBS) may be an alternative for storing and analyzing zopiclone and ACP. Spiked and authentic blood samples and corresponding DBS were analyzed using fully validated LC-MS/MS assays. There was agreement between the measurement of zopiclone from either blood or matching DBS in freshly prepared samples. Results showed that zopiclone was unstable in blood at all storage temperatures except at -20A degrees C. Stability of zopiclone in spiked and authentic blood was increased in DBS compared to matching blood samples stored at the same condition. About 85 {\%} of the initial concentration of zopiclone was still intact in DBS on day 8 at 20A degrees C. ACP was formed from zopiclone in equimolar amounts in both media. Therefore, determination of both zopiclone and ACP may be helpful to estimate the initial concentration in both media. Pre-analytical conditions have a major impact on the recovery of zopiclone from blood. With respect to its known advantages, DBS can be recommended as a valuable alternative for the determination of zopiclone from blood.",
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Degradation of zopiclone during storage of spiked and authentic whole blood and matching dried blood spots. / Jantos, R.; Vermeeren, A.; Sabljic, D.; Ramaekers, J.G.; Skopp, G.

In: International Journal of Legal Medicine, Vol. 127, No. 1, 01.01.2013, p. 69-76.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Degradation of zopiclone during storage of spiked and authentic whole blood and matching dried blood spots

AU - Jantos, R.

AU - Vermeeren, A.

AU - Sabljic, D.

AU - Ramaekers, J.G.

AU - Skopp, G.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Z-drugs such as zopiclone are increasingly involved in forensic cases. Its degradation occurs in solvents and biological fluids. It is assumed that hydrolysis largely accounts for the breakdown of zopiclone in aqueous media. Therefore, a stability study in blood at different storage conditions (-20, 4, 20, and 40A degrees C) was performed to establish changes of the drug's concentration with time, also including its degradation product 2-amino-5-chloropyridine (ACP). As removal of the aqueous phase may stabilize molecules that are prone to hydrolysis, it was assessed whether the use of dried blood spots (DBS) may be an alternative for storing and analyzing zopiclone and ACP. Spiked and authentic blood samples and corresponding DBS were analyzed using fully validated LC-MS/MS assays. There was agreement between the measurement of zopiclone from either blood or matching DBS in freshly prepared samples. Results showed that zopiclone was unstable in blood at all storage temperatures except at -20A degrees C. Stability of zopiclone in spiked and authentic blood was increased in DBS compared to matching blood samples stored at the same condition. About 85 % of the initial concentration of zopiclone was still intact in DBS on day 8 at 20A degrees C. ACP was formed from zopiclone in equimolar amounts in both media. Therefore, determination of both zopiclone and ACP may be helpful to estimate the initial concentration in both media. Pre-analytical conditions have a major impact on the recovery of zopiclone from blood. With respect to its known advantages, DBS can be recommended as a valuable alternative for the determination of zopiclone from blood.

AB - Z-drugs such as zopiclone are increasingly involved in forensic cases. Its degradation occurs in solvents and biological fluids. It is assumed that hydrolysis largely accounts for the breakdown of zopiclone in aqueous media. Therefore, a stability study in blood at different storage conditions (-20, 4, 20, and 40A degrees C) was performed to establish changes of the drug's concentration with time, also including its degradation product 2-amino-5-chloropyridine (ACP). As removal of the aqueous phase may stabilize molecules that are prone to hydrolysis, it was assessed whether the use of dried blood spots (DBS) may be an alternative for storing and analyzing zopiclone and ACP. Spiked and authentic blood samples and corresponding DBS were analyzed using fully validated LC-MS/MS assays. There was agreement between the measurement of zopiclone from either blood or matching DBS in freshly prepared samples. Results showed that zopiclone was unstable in blood at all storage temperatures except at -20A degrees C. Stability of zopiclone in spiked and authentic blood was increased in DBS compared to matching blood samples stored at the same condition. About 85 % of the initial concentration of zopiclone was still intact in DBS on day 8 at 20A degrees C. ACP was formed from zopiclone in equimolar amounts in both media. Therefore, determination of both zopiclone and ACP may be helpful to estimate the initial concentration in both media. Pre-analytical conditions have a major impact on the recovery of zopiclone from blood. With respect to its known advantages, DBS can be recommended as a valuable alternative for the determination of zopiclone from blood.

KW - Zopiclone

KW - Stability

KW - Dried blood spots

KW - Whole blood

KW - LC-MS/MS

KW - BIOANALYTICAL METHOD VALIDATION

KW - DRIVING PERFORMANCE

KW - STABILITY

KW - PLASMA

KW - 2-AMINO-5-CHLOROPYRIDINE

KW - BENZODIAZEPINES

KW - SPECTROMETRY

KW - TOXICOLOGY

KW - MOLECULES

KW - ZALEPLON

U2 - 10.1007/s00414-012-0696-4

DO - 10.1007/s00414-012-0696-4

M3 - Article

VL - 127

SP - 69

EP - 76

JO - International Journal of Legal Medicine

JF - International Journal of Legal Medicine

SN - 0937-9827

IS - 1

ER -