Documentation of a Doxylamine Overdose Death: Quantitation by Standard Addition and Use of Three Instrumental Techniques

Abstract

To answer the question. “Is this death due to a drug overdose?” requires at least that the drug be unequivocally identified and a blood concentration reliably determined. The approach taken in this case as standard addition technique and use of three different chromatographic techniques—high performance liquid chromatography (HPLC), high performance thin—layer chromatography (HP-TLC) and gas chromatography/mass spectrometry (GC/MS). Each of the chromatographies was carried out on the same extract by splitting the residue three ways. HPLC provided a quantitative result which was 1.2 mg/L in blood and HP-TLC and GC/MS confirmed this result with additional quantitative data, information about two metabolites (nordoxylamine and dinordoxylamine) and conclusive identification. Blood nordoxylamine was 0.52 mg/L and doxylamine plus metabolites in urine was 25 mg/L.

Determination of select antidepressants in fish from an effluent‐dominated stream

“…Standard addition eliminates any matrix-effect concerns from the obtained quantitative value by comparing the response ratios from both a spiked and an unspiked replicate of the specimen in question. By adding an identical amount of internal standard to both replicates and also spiking one replicate with a precisely known quantity of the analyte(s) in question, quantitative values are obtained from a simple equation [19]:…”

“…Analyte concentrations in various fish tissues were determined using a standard addition method [19]. Because of potential matrix effects, the analytical response for an analyte extracted from a complex matrix may not be the same as the analytical response for an analyte extracted from a simple matrix.…”

“…Standard addition eliminates any matrix‐effect concerns from the obtained quantitative value by comparing the response ratios from both a spiked and an unspiked replicate of the specimen in question. By adding an identical amount of internal standard to both replicates and also spiking one replicate with a precisely known quantity of the analyte(s) in question, quantitative values are obtained from a simple equation [19]: where C x is the analyte concentration in the specimen, C add is the concentration of drug added to specimen, R x is the peak area ratio of test specimen (no drug added; drug area/internal standard area), and R x+ is the peak area ratio of test specimen with drug added (drug area/internal standard area).…”

Time- and temperature-dependent postmortem concentration changes of the (synthetic) cannabinoids JWH-210, RCS-4, as well as ∆9-tetrahydrocannabinol following pulmonary administration to pigs

“…Thus, national and international guidelines recommend the standard addition approach for quantification of drugs in PM specimens (GTFCh 2018; Jickells and Negrusz 2008;Peters et al 2007;Skopp 2010;SOFT/AAFS 2006). Following this recommendation, this procedure has frequently been applied in quantitative PM studies on the tissue distribution of drugs (Hasegawa et al 2014;Mochizuki et al 2019;Schaefer et al 2017b;Siek and Dunn 1993). In particular in case reports of human fatalities the standard addition method has been used for PM analysis indicating that this is the prevailing analytical procedure in routine PM examination.…”

A Preliminary Study to Predict the Ingested Dose of Doxylamine from its Plasma Concentration in the Korean Patients with Doxylamine Intoxication

“…Fortunately, patients can be usually recovered completely from rhabdomyolysis, if it is recognized and treated promptly so that serious complications such as ARF can be prevented [31]. Most patients with drug intoxication ingested usually multiple drugs, and in the death case with doxylamine overdose, the postmortem blood concentration was 0.7~12 μg/mL [32][33][34] which greatly exceeds the therapeutic range of approximately 0.05~0.15 μg/mL of doxylamine. The blood doxylamine concentration of the Drug Intake (mg) Plasma Drug Concentration (μg/mL) overdose death case was 1.2 μg/mL presented by Siek and Dunn [33] and 12 μg/mL by Bayley et al [34].…”