title: Stability of some atypical antipsychotics in human plasma, haemolysed whole blood, oral fluid, human serum and calf serum.
abstract: Long-term stability data of atypical antipsychotics in different matrices are not widely available. The aim of this work was to assess the stability of amisulpride, aripiprazole and dehydroaripiprazole, clozapine and norclozapine, olanzapine, quetiapine, risperidone and 9-hydroxyrisperidone, and sulpiride in human EDTA plasma, heparinised haemolysed human whole blood, oral fluid, human serum, and newborn calf serum stored in tightly capped plastic containers under a range of conditions. Measurements were performed by LC-MS/MS. Analyte instability was defined as a deviation of 15% or greater from the expected concentration. All analytes were stable following 3 freeze-thaw cycles in human plasma, and were stable in this matrix for at least 5 days at ambient temperature (olanzapine, 3 days); 4 weeks at 2-8°C (olanzapine, 2 weeks), and 2 years at -20°C (except for dehydroaripiprazole, olanzapine, and quetiapine, 1 year). In human serum, aripiprazole, dehydroaripiprazole, norclozapine, olanzapine, quetiapine, risperidone, 9-hydroxyrisperidone, and sulpiride were unstable after 5 days at ambient temperature, 3 weeks at 2-8°C, and 9 months at -20°C. Olanzapine was unstable in whole blood and oral fluid under most conditions studied, although prior addition of ascorbic acid had a moderate stabilising effect. All other analytes were stable in whole blood and oral fluid for at least 2 days at ambient temperature, 1 week at 2-8°C, and 2 months at -20°C (clozapine and norclozapine, 1 month whole blood). These results confirm that plasma (EDTA anticoagulant) is the sample of choice for TDM of atypical antipsychotics. Delayed (more than 1 week) analysis of patient samples should be undertaken with caution, especially with serum and with haemolysed whole blood. With olanzapine, only plasma collected and stored appropriately is likely to give reliable quantitative results.
authors.affiliation: Toxicology Unit, Department of Clinical Biochemistry, Bessemer Wing, King's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK. danielle.fisher@nhs.net
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Fisher
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Partridge
authors.forename: Simon A
authors.initials: SA
authors.lastname: Handley
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Flanagan
mesh_terms: D000077582:Amisulpride; D000818:Animals; D014150:Antipsychotic Agents / Q000032:analysis* / Q000494:pharmacology*; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000032:analysis / Q000494:pharmacology; D002417:Cattle; D002853:Chromatography, Liquid; D003024:Clozapine / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D003987:Dibenzothiazepines / Q000032:analysis / Q000494:pharmacology; D004355:Drug Stability; D005260:Female; D053593:Forensic Toxicology / Q000379:methods; D006461:Hemolysis; D006801:Humans; D007555:Isoxazoles / Q000032:analysis / Q000494:pharmacology; D008297:Male; D000077152:Olanzapine; D000068882:Paliperidone Palmitate; D010879:Piperazines / Q000032:analysis / Q000494:pharmacology; D011743:Pyrimidines / Q000032:analysis / Q000494:pharmacology; D000069348:Quetiapine Fumarate; D015363:Quinolones / Q000032:analysis / Q000494:pharmacology; D015203:Reproducibility of Results; D018967:Risperidone / Q000032:analysis / Q000494:pharmacology; D012463:Saliva / Q000737:chemistry*; D044967:Serum / Q000737:chemistry; D013469:Sulpiride / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D053719:Tandem Mass Spectrometry
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D007555:Isoxazoles; D010879:Piperazines; D011743:Pyrimidines; D015363:Quinolones; D001569:Benzodiazepines; C058272:norclozapine; D000069348:Quetiapine Fumarate; C517414:dehydroaripiprazole; D013469:Sulpiride; D000077582:Amisulpride; D000068180:Aripiprazole; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine; D000068882:Paliperidone Palmitate