The National Coronial Information System (NCIS) is the world's first national Internet-based database of coronial information. It was established in Australia following the recognition by coroners that their mandate for public health and safety could be improved if they could identify previous similar deaths. The NCIS is funded from state, territory, and commonwealth government agencies and overseen by the NCIS Board of Management. A team of ten staff manage the day-to-day operation of the system. The NCIS enables the rapid identification of up-to-date information on deaths investigated by the coroners' jurisdictions in Australia (from July 2000) and New Zealand (from July 2007). It is accessible to death investigators (coroners; forensic, medical, and scientific staff; and police) to assist with death investigation and approved third parties (e.g., researchers). The NCIS contains demographic information about the deceased, contextual information about the circumstances in which the death occurred, the cause and manner of death, and four full text reports generated during the investigation. The NCIS contains information on over 328 000 completed coroners' death investigations across Australia and New Zealand. Approximately 350 death investigators are registered to access the data for their ongoing death investigations, and 235 third party users are registered to utilize the data set in their research. In addition to the utility of the NCIS, this paper describes the rationale and governance structure of the NCIS, the information technology infrastructure, data set, quality assurance framework, and contribution to death and injury prevention.

The National Coronial Information System (NCIS) database contains information about every death reported to an Australian coroner from July 2000 up to today, making it an invaluable source of information for coroners and death investigators alike. With over 80 current research projects across Australia, covering a broad range of public health topics, the database is recognised as an essential national statistical …

Oxycodone is one of the most abused prescription drugs. Iatrogenic factors that lead to oxycodone-related death, such as mis-prescribing, present an opportunity for death prevention if identified early. This study investigated deaths involving oxycodone in Australia to explore potentially inappropriate prescribing and the coroner's investigation. The National Coronial Information System identified cases from 2001 to 2011 where oxycodone was detected by toxicological analysis. There were 806 oxycodone-related deaths, with a significant increase in the 11-year period, from 21 deaths in 2001, up almost sevenfold in 2011 (139 deaths). Most deaths were caused by combined drug toxicity (63.4%) or oxycodone toxicity alone (11.8%). Most individuals were male (59.1%), aged 35-44 years (26.7%), who died unintentionally (56.4%), with mental illness (52.1%) and/or a history of acute or chronic pain (46.2%). 312 cases (39%) described a legitimate prescription for oxycodone, of which most involved non-cancer related chronic pain. About three quarters of the indications were deemed appropriate. There were at least 43 different indications treated with oxycodone that were inappropriate. The majority of oxycodone-related cases involved minor to no description of the drugs involved (n = 600; 74.4%). A moderate description of oxycodone involvement was given in 162 cases (20.1%), while only 44 cases (5.5%) involved a thorough examination and recommendations from the coroners on oxycodone and other drugs involved in death. This study emphasized the need for medical practitioners to exercise caution when prescribing oxycodone and for coroners to provide more consistent and detailed information regarding drug use, in order to identify and implement preventive strategies.

Objectives: To examine trends in codeine-related mortality rates in Australia, and the clinical and toxicological characteristics of codeine-related deaths.Design and setting: Analysis of prospectively collected data from the National Coronial Information System on deaths where codeine toxicity was determined to be an underlying or contributory cause of death. The study period was 2000-2013.Main outcome measures: Population-adjusted numbers (per million persons) of (1) codeine-related deaths, classified by intent (accidental or intentional); and (2) heroin-and Schedule 8 opioid-related deaths (as a comparator).Results: The overall rate of codeine-related deaths increased from 3.5 per million in 2000 to 8.7 per million in 2009. Deaths attributed to accidental overdoses weremore common (48.8%) than intentional deaths (34.7%), and their proportion increased during the study period. High rates of prior comorbid mental health (53.6%), substance use (36.1%) and chronic pain (35.8%) problems were recorded for these deaths. For every two Schedule 8 opioid-related deaths in 2009, there was one codeine-related death. Most codeine-related deaths (83.7%) were the result of multiple drug toxicity.Conclusions: Codeine-related deaths (with and without other drug toxicity) are increasing as the consumption of codeine-based products increases. Educational messages are needed to better inform the public about the potential harms of chronic codeine use, especially in the context of polypharmacy.

The aim of this study was to develop an LC-MS/MS based screening technique that covers a broad range of acidic and neutral drugs and poisons by combining a small sample volume and efficient extraction technique with simple automated data processing. After protein precipitation of 100μL of whole blood, 132 common acidic and neutral drugs and poisons including non-steroidal anti-inflammatory drugs, barbiturates, anticonvulsants, antidiabetics, muscle relaxants, diuretics and superwarfarin rodenticides (47 quantitated, 85 reported as detected) were separated using a Shimadzu Prominence HPLC system with a C18 separation column (Kinetex XB-C18, 4.6mm×150mm, 5μm), using gradient elution with a mobile phase of 25mM ammonium acetate buffer (pH 7.5)/acetonitrile. The drugs were detected using an ABSciex(®) API 2000 LC-MS/MS system (ESI+ and -, MRM mode, two transitions per analyte). The method was fully validated in accordance with international guidelines. Quantification data obtained using one-point calibration compared favorably to that using multiple calibrants. The presented LC-MS/MS assay has proven to be applicable for determination of the analytes in blood. The fast and reliable extraction method combined with automated processing gives the opportunity for high throughput and fast turnaround times for forensic and clinical toxicology.

The post mortem redistribution of ten commonly prescribed antipsychotic drugs (APs) was investigated. Femoral blood was collected from 273 cases at admission to mortuary (AD) and at post-mortem (PM). The PM samples were collected at various times up to nine days after admission and the sample pairs analysed using LC-MS/MS. The drugs included in this study were 9OH-risperidone (paliperidone), amisulpride, chlorpromazine, clozapine, haloperidol, olanzapine, promethazine, quetiapine, risperidone, and zuclopenthixol. Haloperidol, quetiapine and risperidone showed minimal changes between AD and PM specimens, whereas the majority of drugs showed significant changes between the sample pairs collected at different time points post mortem (p<0.01) in addition to an average concentration change greater than the uncertainty of measurement of the applied method. Average increases in blood concentrations after admission to the mortuary ranged up to 112% (chlorpromazine and olanzapine) but also decreases up to -43% (9OH-risperidone) were seen. There were large standard deviations between sample pairs and substantial day-to-day unpredictable changes that highlight the difficulty in the interpretation of drug concentrations post-mortem. Based on the presented data, we recommend that specimens for toxicological analysis should to be taken as soon as possible after admission of a deceased person to the mortuary in order to minimise the effects of the PM interval on the drug concentration in blood.

Antipsychotic drugs (APs) are prescribed for a wide range of psychotic illnesses. With more than 35 APs currently available worldwide, this drug class has rapidly gained importance in both clinical and forensic settings. On account of their chemical properties, many APs are present in human specimens at very low concentrations, which complicate their detection using standard gas chromatography–mass spectrometry (GC‐MS) procedures that often cannot provide the required sensitivity. Recent advances in liquid chromatography‐(tandem) mass spectrometry LC‐MS(/MS) technology have enabled accurate detection and quantification of these compounds in various human specimens, indicated by the increasing number of published methods. Method validation has been a particular focus of analytical chemistry in recent times. Recommendations set by several guidance documents are now widely accepted by the toxicology community, as reflected by the guidelines drafted by leading toxicological societies. This review provides a critical review of single‐stage and tandem LC‐MS procedures for the detection and quantification of APs, with a particular emphasis on appropriate method validation. The quality of published methods is inconsistent throughout the literature. While the majority of authors incorporate some validation experiments in their respective method development, a large number of published methods lack essential components of method validation, which are considered mandatory according to the guidelines. If adapting a method for the detection of APs for use in a laboratory, analysts should ensure successful validation experiments for appropriateness and completeness have been conducted, and perform additional experiments when indicated. Copyright © 2012 John Wiley & Sons, Ltd.

Olanzapine (OLZ) is amongst the most commonly prescribed antipsychotic drugs and is associated with substantial instability. The aim of this study was to investigate the instability of OLZ and to identify the degradants formed from its breakdown. Three experiments were conducted to monitor the degradation of OLZ and the formation of degradants in blood (1), water (2), and post-extraction at 4 °C (3). All three sample sets were analysed in duplicate and repeated in the absence (A) and presence (B) of 0.25% ascorbic acid. One degradant was identified in sample sets 2A and 3A with m/z 329 and confirmed as 2-hydroxymethyl-OLZ (2-OH-OLZ) using LC-MS techniques. The addition of 0.25% ascorbic acid slowed the degradation of OLZ down in all three experiments and inhibited the formation of 2-OH-OLZ in sample sets 2A and 3A. To investigate the influence of oxygen on the degradation of OLZ and the formation of 2-OH-OLZ in water, an additional experiment (4) was conducted. Sample sets were prepared containing different vortexing or sonication steps in order to alter the oxygen content in the samples. Statistical analysis confirmed that degradation increased significantly following vortexing for 1 min while sonication did not affect the rate of degradation of OLZ further suggesting the involvement of oxygen in the degradative processes. 2-OH-OLZ was only identified as a degradant of OLZ in aqueous solutions. It also degrades over time but its product is currently unknown and is under investigation.

The stability of 30 common antipsychotics (APs) in spiked whole blood was investigated over ten weeks in a preliminary experiment (designated “P experiment”). Pools of blank blood spiked with drugs at two different therapeutic levels were stored at four different temperatures: 20°C, 4°C, −20°C, and −60°C and extracted once weekly in duplicate, using a previously published method. A loss of >15% of the initial drug concentration was considered to indicate possible instability and the respective drugs were selected for further investigation in a final experiment (designated “F experiment”).Eight APs (chlorpromazine, chlorprothixene, fluspirilene, droperidol, olanzapine, thioridazine, triflupromazine, and ziprasidone) were incorporated into the F experiment. The same conditions were used in both experiments, however only a high therapeutic drug concentration was chosen for the F experiment and the storage time was extended to 20 weeks.All drugs of interest in the F experiment showed significant losses after 20 weeks of storage under at least one storage condition. The most notable results involved olanzapine, where losses of almost 100% in all storage temperatures were observed. Drug degradation in fluspirilene samples was significant after 20 weeks under all storage conditions. Overall, extensive degradation was seen with approximately 80% drug loss when stored at 20°C and 4°C with samples also seriously affected by degradation of up to 50% when stored at −20°C and −60°C, respectively. Ziprasidone remained stable when stored at 4°C, −20°C, and −60°C over 9 weeks, however significant degradation was observed when stored at 20°C, with a loss of almost 100% after 20 weeks of storage.The time period and temperature of storage of biological samples can have a significant influence on the stability of several APs. It is therefore important to be aware of potential changes in drug concentrations during storage when interpreting analytical results.

Over the last decade, the prescription rates of antipsychotic (AP) drugs have increased worldwide. Studies have shown that the risk of sudden cardiac death is threefold higher among patients treated with APs. To investigate the presence of APs in postmortem cases, a liquid chromatography (LC)-MS/MS method was developed using only 0.1 ml of blood sample with 10 microl of internal standard (IS) (haloperidol-d(4), 1 microg/ml). After the addition of 0.2 ml of Trizma buffer, the blood sample was extracted using liquid-liquid extraction (LLE) with 1 ml of 1-chlorobutane for 5 min on a shaker at 1500 rpm. After centrifugation at 12,000 rpm for 1 min, the separated solvent layer was transferred to an autosampler vial and evaporated to dryness under N(2). The residue was reconstituted in 0.05 ml acetonitrile containing 0.1% formic acid, vortexed for 30 s and an additional 0.45 ml of 50 mmol/l ammonium formate pH 3.5 was added and the sample vortexed; 0.1 ml of the final extract was injected into a Shimadzu Prominence HPLC system, with detection of drugs achieved using an Applied Biosystems 3200 Q-TRAP LC-MS/MS system equipped with a Turbo V ion source [electron spray ionization (ESI), multiple reaction monitoring (MRM) mode]. The method has been validated according to international guidelines and was found to be selective for all tested compounds. Calibration was satisfactory for all drugs, except olanzapine, from subtherapeutic to toxic concentrations. The lower limits of quantifications (LLOQs) corresponded to the lowest concentrations used for the calibration curves. With the exception of the lowest concentrations of bromperidol, buspirone and perphenazine, accuracy data were within the acceptance interval of +/- 15% (+/- 20% at LLOQ) of the nominal values for all drugs. The method has been proven to be useful for the routine analysis of APs in postmortem blood samples.

Antipsychotic drugs are frequently associated with sudden death investigations. Detection of these drugs is necessary to establish their use and possible contribution to the death. LC–MS(MS) methods are common; however accurate and precise quantification is assured by using validated methods. This study compared extraction efficiency and matrix effects using common liquid–liquid and solid-phase extraction procedures in both ante-mortem and post-mortem specimen using LC–MS–MS. Extraction efficiencies and matrix effects were determined in five different blank blood specimens of each blood type. The samples were extracted using a number of different liquid–liquid extraction methods and compared with a standard mixed-mode solid-phase extraction method. Matrix effects were determined using a post-extraction addition approach—the blank blood specimens were extracted as described above and the extracts were reconstituted in mobile phase containing a known amount of analytes. The extraction comparison of ante-mortem and post-mortem blood showed considerable differences, in particular the extraction efficiency was quite different between ante-mortem and post-mortem blood. Quantitative methods used for determination of antipsychotic drugs in post-mortem blood should establish that there are no differences in extraction efficiency and matrix effects, particularly if using ante-mortem blood as calibrator.