Diclofenac Concentrations in Post-Mortem Specimens—Distribution, Case Reports, and Validated Method (UHPLC-QqQ-MS/MS) for Its Determination

Abstract

The aim of the research was to establish a sensitive method for the quantification of diclofenac in postmortem samples. The developed method was applied in six cases: three fetuses in which the use of abortion pills by their mothers was suspected, one case of duodenal ulcer perforation, one case of traffic accident with fatal outcome, and one acute renal failure in which the distribution of diclofenac was examined. The analyses were performed using liquid–liquid extraction of postmortem samples and the quantification of diclofenac via ultra-high performance liquid chromatography, coupled with triple quadrupole tandem mass spectrometry. Gradient elution using a C18 column was applied. Electrospray ionization measurement in positive multiple reaction monitoring mode was used. Diclofenac-d4 was used as an internal standard. The validation parameters were as follows: lower limit of quantification: 0.5 ng/mL, linearity of calibration curve: 0.5–500 ng/mL, intra- and interday accuracies and precisions: not greater than 15%; recovery values: 72.0–102.2%, and matrix effect: 2.2–28.0%. The developed method enabled the determination of diclofenac in human postmortem biological fluids (blood, urine, vitreous humor, bile, and stomach content), tissues (placenta, kidney, liver, and heart), and in exhumated fetus bones, with high recovery, sensitivity, precision, and accuracy.

Determination of Mifepristone (RU-486) and Its Metabolites in Maternal Blood Sample after Pharmacological Abortion

“…This is most likely related to the rapid metabolism of misoprostol, which makes it undetectable within a short time after ingestion [ 17 ]. Diclofenac, an ingredient that is often present with misoprostol in pills [ 18 ], was also not detected. The biological material from the fetus was not provided to our laboratory for toxicological analysis.…”

Forensic Toxicological Aspects of Misoprostol Use in Pharmacological Abortions

“…Toxicological analysis of the placenta revealed diclofenac at a concentration of 305.6 µg/g and misoprostol acid in a concentration of 2332 pg/g. Diclofenac concentrations in the above-mentioned biological materials collected in both cases were quantified by the method described earlier by Szpot et al [ 29 ].…”

“…The problem of the instability of misoprostol acid in biological material is especially important when testing postmortem material. The corpses of fetuses in cases of illegal abortion could be found, for example, on the sidewalk (Case 2), in garbage cans, sewage farm [ 29 ], etc., where external conditions are highly variable and tanatochemical processes can lead to the degradation of a misoprostol acid. Cases of misoprostol use for abortion purposes by women without specialized medical care (as described in this paper) confirm that, besides the enormous risks, such a hazardous method of pregnancy termination is unfortunately still common (especially in countries with restrictive abortion laws).…”

Determination of Prostaglandins (Carboprost, Cloprostenol, Dinoprost, Dinoprostone, Misoprostol, Sulprostone) by UHPLC-MS/MS in Toxicological Investigations

“…Diclofenac dose per sample were as follows: 67.7 mg (sample 1), 65.3 mg (sample 2) and 67.3 mg (sample 3). Diclofenac was quantified with the use of the method published earlier [21]. No antifungal substances were found in the tested samples.…”

“…In toxicological examinations, blood and urine samples are collected most often. However, it is worth noticing alternative materials, i.e., oral fluid, hair, meconium, breast milk [19], vitreous humor, bone marrow [20], exhumated samples (e.g., bones) [21] and entomological specimens [22]. In this paper's authentic casework, we present a toxicological analysis of pills collected during gynecological examination.…”