HPLC–ESI-MS/MS validated method for simultaneous quantification of zopiclone and its metabolites, N-desmethyl zopiclone and zopiclone-N-oxide in human plasma

Zopiclone degradation in biological samples : Characteristics and consequences in forensic toxicology

“…Freeze-thaw stability tests verified that ZOP was stable in spiked human plasma for three freeze-thaw cycles [118,129] but stability for five freezethaw cycles has also been reported [131]. Short-term or in process stability tests give no evidence of degradation in plasma when quality control samples were stored at room temperature for 12 h [131] or 24 h [129]. No loss of ZOP was detected when blood samples (plasma) was stored at 4-8°C for less than 6 h. The concentration of ZOP in blood was reduced by 25% and 29% for the (-)-and (+)-enantiomers, respectively, after 20 h storage at ambient temperature [119].…”

“…Several analytical methods, including high performance liquid chromatography (HPLC), gas chromatography (GC), gas chromatography mass spectrometry (GC-MS), liquid chromatography mass spectrometry (LC-MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS), have been developed for the identification and quantification of ZOP in whole blood, serum and/or plasma [118,[120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136]. Some assays (HPLC, LC-MS, LC-MS/MS) have also been developed to separate and determine ZOP [127,[137][138][139] and/or its metabolites (NDZOP and ZOPNO) in urine [140][141][142].…”

“…A couple of methods have been developed to include also the analysis of ZOP metabolites NDZOP and/or ZOPNO in plasma. One method (HPLC) has been reported to detect ZOP and its major metabolite NDZOP [129], and the other both of metabolites together with the parent drug [131]. Stereo specific methods [LC, capillary electrophoresis (CE), radioimmunoassay (RIA), HPLC, LC-MS/MS] have been developed to separate the enantiomers in urine [143][144][145] and in plasma [119,[146][147][148].…”

“…Studies of the stability of ZOP have also been carried out from stability experiments in connection with method development and validation. Long-term stability tests with spiked human plasma showed that ZOP was stable for one month [118,129], for 74 days [131] and for six months [119] when stored at -20°C or lower. Freeze-thaw stability tests verified that ZOP was stable in spiked human plasma for three freeze-thaw cycles [118,129] but stability for five freezethaw cycles has also been reported [131].…”

“…Long-term stability tests with spiked human plasma showed that ZOP was stable for one month [118,129], for 74 days [131] and for six months [119] when stored at -20°C or lower. Freeze-thaw stability tests verified that ZOP was stable in spiked human plasma for three freeze-thaw cycles [118,129] but stability for five freezethaw cycles has also been reported [131]. Short-term or in process stability tests give no evidence of degradation in plasma when quality control samples were stored at room temperature for 12 h [131] or 24 h [129].…”