Quantitative determination of valproic acid in postmortem blood samples--evidence of strong matrix dependency and instability
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Quantitative determination of valproic acid in postmortem blood samples--evidence of strong matrix dependency and instability. / Kiencke, Verena; Andresen-Streichert, Hilke; Müller, Alexander; Iwersen-Bergmann, Stefanie.
in: INT J LEGAL MED, Jahrgang 127, Nr. 6, 01.11.2013, S. 1101-7.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Quantitative determination of valproic acid in postmortem blood samples--evidence of strong matrix dependency and instability
AU - Kiencke, Verena
AU - Andresen-Streichert, Hilke
AU - Müller, Alexander
AU - Iwersen-Bergmann, Stefanie
PY - 2013/11/1
Y1 - 2013/11/1
N2 - Most of the daily work of forensic toxicologists deals with fatal cases resulting from overdoses of licit and illicit drugs. However, another reason for fatalities in patients suffering from epilepsy can be undetectable or subtherapeutic levels of antiepileptic drugs. Some studies have shown a correlation between "sudden unexpected death in epilepsy" (SUDEP) and the ineffective treatment of epilepsy. Low levels of antiepileptic drugs may be a risk factor for SUDEP. The death of a psychiatric patient also suffering from epilepsy inspired the investigation. Subsequent to the death of the patient, the doctor was accused of providing inadequate therapy for epilepsy. The patient was to be treated with valproic acid. We developed and validated a simple method of determining valproic acid levels by gas chromatography-mass spectrometry for serum, but a transfer of the method from serum to postmortem whole blood failed. The method had to be modified and revalidated for postmortem whole blood specimens. A stability study of valproic acid in postmortem blood was conducted, showing a decline of valproic acid levels by 85 % after storage at room temperature for 28 days. During the storage time, the blood samples showed changes in consistency. Depending on the stage of decomposition, it is necessary to perform a determination by standard addition with an equilibration time of 4 h before extraction to achieve reliable results. For a proper interpretation of quantitative results, it is necessary to keep the postmortem decline of valproic acid concentrations in mind.
AB - Most of the daily work of forensic toxicologists deals with fatal cases resulting from overdoses of licit and illicit drugs. However, another reason for fatalities in patients suffering from epilepsy can be undetectable or subtherapeutic levels of antiepileptic drugs. Some studies have shown a correlation between "sudden unexpected death in epilepsy" (SUDEP) and the ineffective treatment of epilepsy. Low levels of antiepileptic drugs may be a risk factor for SUDEP. The death of a psychiatric patient also suffering from epilepsy inspired the investigation. Subsequent to the death of the patient, the doctor was accused of providing inadequate therapy for epilepsy. The patient was to be treated with valproic acid. We developed and validated a simple method of determining valproic acid levels by gas chromatography-mass spectrometry for serum, but a transfer of the method from serum to postmortem whole blood failed. The method had to be modified and revalidated for postmortem whole blood specimens. A stability study of valproic acid in postmortem blood was conducted, showing a decline of valproic acid levels by 85 % after storage at room temperature for 28 days. During the storage time, the blood samples showed changes in consistency. Depending on the stage of decomposition, it is necessary to perform a determination by standard addition with an equilibration time of 4 h before extraction to achieve reliable results. For a proper interpretation of quantitative results, it is necessary to keep the postmortem decline of valproic acid concentrations in mind.
U2 - 10.1007/s00414-013-0843-6
DO - 10.1007/s00414-013-0843-6
M3 - SCORING: Journal article
C2 - 23536197
VL - 127
SP - 1101
EP - 1107
JO - INT J LEGAL MED
JF - INT J LEGAL MED
SN - 0937-9827
IS - 6
ER -