Postmortem distribution of mepirapim and acetyl fentanyl in biological fluid and solid tissue specimens measured by the standard addition method.

PURPOSE: Mepirapim is a new synthetic cannabinoid. We previously reported that the concentrations of unchanged mepirapim in whole blood and urine were much higher than those of other synthetic cannabinoids. To determine the postmortem distribution of mepirapim and acetyl fentanyl in the deceased individual, we established a standard addition method for detailed analysis by liquid chromatography-mass spectrometry (LC-MS) for quantification of these drugs. METHODS: The LC-MS method was fully validated for linearity, extraction recovery, matrix effect and repeatability. RESULTS: Good linearities, extraction recoveries, matrix effects and repeatabilities were shown for both target compounds in all specimens. The concentrations of mepirapim and acetyl fentanyl in three body fluid specimens and 12 solid tissue specimens were measured. For mepirapim, the highest concentrations were found in the liver and kidney, and the concentrations in the blood and urine specimens were one order of magnitude lower than the high concentrations in the solid tissues except the psoas major muscle. For acetyl fentanyl, the highest concentrations were found in the myocardium, spleen and kidney, and the concentrations in the body fluid specimens were also one order of magnitude lower than the highest concentrations in the solid tissues. There were concentration differences of mepirapim and acetyl fentanyl among the regions of the brain. CONCLUSIONS: The concentration of unchanged mepirapim in urine was much higher than those of other synthetic cannabinoids; the higher dosage, urinary excretion, metabolisms and/or pharmacokinetics of mepirapim may be quite different from those of other synthetic cannabinoids.

Identification and quantification of mepirapim and acetyl fentanyl in authentic human whole blood and urine samples by GC-MS/MS and LC-MS/MS.

PURPOSE: We encountered a curious case in which two male subjects self-administered mepirapim plus acetyl fentanyl by different routes, i.e., intravenously and by inhalation. We have thus established a detailed procedure for quantification of mepirapim and acetyl fentanyl in whole blood and urine specimens using gas chromatography (GC)-tandem mass spectrometry (MS/MS). METHODS: The GC-MS/MS method was validated for linearity, extraction recovery, accuracy, and precision. Liquid chromatography-MS/MS was also used for identification of the target compounds. RESULTS: Good linearity and reproducibility were achieved in the range of 20-1000 ng/g for both target compounds in both matrices. The concentrations of mepirapim in heart whole blood, femoral vein whole blood, and urine of the deceased individual with administration by intravenous injection were 593, 567, and 527 ng/g, respectively; those of acetyl fentanyl were 155, 125, and 126 ng/g, respectively. The mepirapim and acetyl fentanyl concentrations in the urine specimen of the surviving individual who had administered them by inhalation were 4900 and 570 ng/g, respectively. CONCLUSIONS: To our knowledge, with the exception of a brief mention of a mepirapim concentration in a serum sample in emergency medicine, there are no reported data on the identification and quantification of mepirapim in biological samples. Mepirapim is a new synthetic cannabinoid. The concentration profiles of unchanged mepirapim in whole blood and urine were quite different and unique. A detailed clarification of such uniqueness is under way in our laboratory.

Development of double cylindrical dielectric barrier discharge ion source.

This paper deals with the dielectric barrier discharge (DBD) ion source composed of the outer cylindrical dielectric tube and the inner grounded metallic tube electrode. The sample gas is supplied through the inner ceramic tube. In this ion source, the DBD plasma is localized in the DBD tube so that the sample gases can be ionized just outside of the ceramic tube by the DBD excited helium gas without being exposed in the plasma jet. Besides, ambient air does not take part in the ionization of the sample vapor because ionization takes place inside the DBD ion source. Thus, this method is totally free from contaminants in ambient air. It was found that this ion source is capable of soft, high-sensitivity, and reproducible ionization. Application of this technique to the analysis of methamphetamine, carbaryl and basil leaf was given.

Development of ambient sampling chemi/chemical ion source with dielectric barrier discharge.

The development of a new configuration of chemical ionization (CI)-based ion source is presented. The ambient air containing the gaseous sample is sniffed into an enclosed ionization chamber which is of sub-ambient pressure, and is subsequently mixed with metastable species in front of the ion inlet of the mass spectrometer. Metastable helium atoms (He*) are used in this study as the primary ionizing agents and are generated from a dielectric barrier discharge (DBD) source. The DBD is powered by an AC high-voltage supply and the configuration of the electrodes is in such a way that the generated plasma is confined within the discharge tube and is not extended into the ionization chamber. The construction of the ion source is simple, and volatile compounds released from the bulky sample can also be analyzed directly by approaching the sample to the sampling nozzle. When combined with heated nitrogen or other desorption methods, its application can also be extended to non-volatile compounds, and the consumption for helium can be kept minimum solely for maintaining the stable discharge and gas phase ionization. Applications to non-proximate sample analysis, direct determination of active ingredients in drug tablets and the detection of trace explosive such as hexamethylene triperoxide diamine are demonstrated.

Rapid detection of drugs in biofluids using atmospheric pressure chemi/chemical ionization mass spectrometry.

We have demonstrated that, with simple pH adjustment, volatile drugs such as methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), ketamine, and valproic acid could be analyzed rapidly from raw biofluid samples (e.g. urine and serum) without dilution, or extraction, using atmospheric pressure ionization. The ion source was a variant type of atmospheric pressure chemical ionization (APCI) that used a dielectric barrier discharge (DBD) to generate the metastable helium gas and reagent ions. The sample solution was loaded in a disposable glass pipette, and the volatile compounds were purged by nitrogen gas to be reacted with the metastable helium gas. The electrodes of the DBD were arranged in such a way that the generated glow discharge was confined within the discharge tube and was not exposed to the analytes. A needle held at 100-500 V was placed between the ion-sampling orifice and the discharge tube to guide the analyte ions into the mass spectrometer. After pH adjustment of the biofluid sample, the amphiphilic drugs were in the form of a water-insoluble oil, which could be concentrated on the liquid surface. By gentle heating of the sample to increase the evaporation rate, rapid and sensitive detection of these drugs in raw urine and serum samples could be achieved in less than 2 min for each sample.

Methamphetamine body packer: acute poisoning death due to massive leaking of methamphetamine.

We encountered three methamphetamine (MA) body packers presenting simultaneously, one of whom died. Three Nigerian men (39, 35, and 37 years old) who attempted to smuggle were found to contain 35 (498 g), 21 (292 g), and 5 packages (73 g) of methamphetamine hydrochloride (MA-HCl) in their stomachs, respectively. Packages were wrapped with plastic film and Scotch tape. The 39-year-old man died with acute poisoning from c. 20 g of MA-HCl that had leaked from the packages into the stomach. His plasma MA concentration was 8.6 microg/mL when he was hospitalized (17 h before his death). Autopsy findings showed extreme pulmonary congestion and edema as well as moderate hepatic edema and several petechiae. Quantitative analysis was performed by gas chromatography/mass spectrometry. Extremely high concentrations of MA and its metabolite amphetamine (AP) were found in cardiac blood (63.5 microg/mL and 1.2 microg/mL), urine (4,518 microg/mL and 72.4 microg/mL), gastric contents (8,490 microg/mL and 16.9 microg/mL), and in all other autopsy samples. These high concentrations confirmed that the cause of death was acute MA poisoning. Furthermore, impurity-profiling analysis of the seized MA revealed that the MA smuggled by the three suspects originated from the same batch.