scholarly journals Fatal, Intentional Overdose of Ranolazine: Post-Mortem Distribution of Parent Drug and its Major Metabolite

2020 ◽  
Author(s):  
Rossella Gottardo ◽  
Zeno De Battisti ◽  
Federico Busetti ◽  
Matilde Murari ◽  
Franco Tagliaro
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Drugs Of Abuse ◽  
Biological Fluids ◽  
Sodium Current ◽  
Parent Drug ◽  
Major Metabolite ◽  
Post Mortem ◽  
Cardiac Blood ◽  
Femoral Blood

ABSTRACT Purpose Ranolazine is a selective inhibitor of the late inward sodium-current, approved for the treatment of chronic angina. Here, we report a case of a possibly suicidal death due to acute ranolazine overdosing. A 41-year-old woman was found unconscious by her son and was urgently admitted to the Intensive Care Unit. She had ingested an unknown amount of ranolazine tablets. Seventeen hours after admission, the patient died. An autopsy was performed 4 days post-mortem. Methods A routine screening analysis for drugs of abuse and medicinal drugs performed by liquid chromatography ion trap mass spectrometry on autopsy samples of biological fluids did not detect any relevant presence of toxicologically relevant compounds, but ranolazine. A quantitative analysis was then carried out by liquid chromatography- QqQ mass spectrometry in order to quantify ranolazine and its major metabolite O-desmethyl-ranolazine in biological fluids and organs. Results Ranolazine concentrations in biological fluids were as follows: cardiac blood, 19.5 μg/mL; femoral blood, 12.3 μg/mL; bile, 0.87 μg/mL and vitreous humor, 15.4 μg/mL. For O-desmethyl-ranolazine the concentrations in cardiac blood, femoral blood, bile and vitreous were 10.7 μg/mL; 9.6 μg/mL; 11,103 μg/mL and 11.4 μg/mL, respectively. Conclusions The cause of death was attributed to ranolazine overdosing. To the best of our knowledge, this is the first report of a fatality associated with ranolazine, in which the postmortem distribution of ranolazine and its metabolite has been quantitatively assessed. The present study can therefore provide useful information for interpretation of the causes and mechanisms of death in ranolazine associated fatalities.

A Review of Analytical Methods for the Determination of Tibolone: Pharmacokinetics and Pharmaceutical Formulations Analysis and Application in Doping Control

2020 ◽  
Vol 17 (1) ◽  
pp. 31-39
Author(s):  
Marilene Lopes Ângelo ◽  
Fernanda de Lima Moreira ◽  
Ana Laura Araújo Santos ◽  
Hérida Regina Nunes Salgado ◽  
Magali Benjamim de Araújo
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Analytical Methods ◽  
Estrogenic Activity ◽  
Biological Fluids ◽  
Pharmaceutical Formulations ◽  
Doping Control ◽  
Specific Effects ◽  
In Doping

Background:: Tibolone is a synthetic steroid commercialized by Organon under the brand name Livial (Org OD14), which is used in hormone therapy for menopause management and treatment of postmenopausal osteoporosis. Tibolone is defined as a selective tissue estrogenic activity regulator (STEAR) demonstrating tissue-specific effects on several organs such as brain, breast, urogenital tract, endometrium, bone and cardiovascular system. Aims:: This work aims to (1) present an overview of important published literature on existing methods for the analysis of tibolone and/or its metabolites in pharmaceutical formulations and biological fluids and (2) to conduct a critical comparison of the analytical methods used in doping control, pharmacokinetics and pharmaceutical formulations analysis of tibolone and its metabolites. Results and conclusions: : The major analytical method described for the analysis of tibolone in pharmaceutical formulations is High Pressure Liquid Chromatography (HPLC) coupled with ultraviolet (UV) detection, while Liquid Chromatography (LC) or Gas Chromatography (GC) used in combination with Mass Spectrometry (MS) or tandem mass spectrometry (MS/MS) is employed for the analysis of tibolone and/or its metabolites in biological fluids.

scholarly journals Quantification of Serum and Urinary S-Adenosylmethionine and S-Adenosylhomocysteine by Stable-Isotope-Dilution Liquid Chromatography-Mass Spectrometry

2004 ◽  
Vol 50 (2) ◽  
pp. 365-372 ◽  
Author(s):  
Sally P Stabler ◽  
Robert H Allen
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Stable Isotope ◽  
Isotope Dilution ◽  
Biological Fluids ◽  
Internal Standard ◽  
Fractional Excretion ◽  
Liquid Chromatography Mass Spectrometry ◽  
Stable Isotope Dilution ◽  
Chromatography Mass Spectrometry

Abstract Background: We have developed an assay that uses stable-isotope-dilution liquid chromatography–mass spectrometry to assess S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in body fluids to investigate the relationship of these metabolites to hyperhomocysteinemia. Methods: Commercially obtained SAM (D3 methyl) and 13C5-SAH uniformly labeled in the adenosyl moiety, which was synthesized using S-adenosylhomocysteine hydrolase, were added to samples followed by perchloric acid protein precipitation, C18 chromatography, and analysis by liquid chromatography–mass spectrometry with quantification by comparison of the areas of internal standard and endogenous peaks. Results: Estimates of intraassay imprecision (CV) were 5% and 17% for SAM and SAH, respectively (n = 10). SAM decreased and SAH increased in serum and plasma samples at both 4 °C and room temperature over 80 h. SAM and SAH were unstable in samples stored longer than 2 years at −20 °C. In 48 volunteers, the estimated reference intervals [from mean (2 SD) of log-transformed data] for serum SAM and SAH were 71–168 and 8–26 nmol/L, respectively. Fractional excretion of SAM was higher than that of SAH, and the urinary SAM:SAH ratio was much higher than the serum or erythrocyte SAM:SAH ratios. Conclusions: Stable-isotope-dilution liquid chromatography–mass spectrometry can be used to quantify SAM and SAH in biological fluids and tissues. Sample handling and storage must be stringently controlled for any epidemiologic or clinical use of such assays.

Sign in / Sign up

Export Citation Format

Share Document