b2f2433c76d54462be3d2c6bef7c8a4f pmc_9736016.pdf 2d2a688de29d1dc1136630b2ea7cef27e1146283 pmc_9736016.pdf 0d042cc39c18bd4a85eb553f3f771ed29252bc56d6576838e190aca111e37355 pmc_9736016.pdf Title: Methylone and MDMA Pharmacokinetics Following Controlled Administration in Humans Subject: The aim of this study is to define, for the first time, human methylone and HMMC plasma pharmacokinetics following controlled administration of 50–200 mg methylone to 12 male volunteers. A new LC-MS/MS method was validated to quantify methylone, MDMA, and their metabolites in plasma. The study was a randomized, cross-over, double-blinded and placebo-controlled study, with a total of 468 plasma samples collected. First, 10 L of MDMA-d5, MDA-d5 and methylone-d3 internal standards were added to 100 L of plasma. Two mL of chloroform and ethyl acetate 9:1 (v/v) were then added, mixed well and centrifuged. The supernatant was fortified with 0.1 mL acidified methanol and evaporated under nitrogen. Samples were reconstituted with a mobile phase and injected into the LC-MS/MS instrument. The method was fully validated according to OSAC guidelines (USA). Methylone plasma concentrations increased in a dose-proportional manner, as demonstrated by the increasing maximum concentration (Cmax) and area under the curve of concentrations (AUC). Methylone Cmax values were reported as 153, 304, 355 and 604 ng/mL, AUC0–24 values were reported as 1042.8, 2441.2, 3524.4 and 5067.9 hng/mL and T1/2 values as 5.8, 6.4, 6.9 and 6.4 h following the 50, 100, 150 and 200 mg doses, respectively. Methylone exhibited rapid kinetics with a Tmax of 1.5 h for the 50 mg dose and 2 h approximately after all the other doses. HMMC exhibited faster kinetics compared to methylone, with a Cmax value that was 10–14-fold lower and an AUC0–24 value that was 21–29-fold lower. Methylone pharmacokinetics was linear across 50–200 mg oral doses in humans, unlike the previously described non-linear oral MDMA pharmacokinetics. An LC-MS/MS method for the quantification of methylone, MDMA and their metabolites in human plasma was achieved. Methylone exhibited linear pharmacokinetics in humans with oral doses of 50–200 mg. Keywords: methylone; MDMA; pharmacokinetics; humans; LC-MS/MS Author: Lourdes Poyatos, Alfredo Fabrizio Lo Faro, Diletta Berardinelli, Giorgia Sprega, Sara Malaca, Simona Pichini, Marilyn A. Huestis, Esther Papaseit, Clara Pérez-Mañá, Francesco Paolo Busardò and Magí Farré Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Nov 25 05:20:48 2022 CET ModDate: Fri Nov 25 08:52:25 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 839069 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MPDLZD+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 CAMXTK+EURM10 Type 1 Builtin yes yes no 15 0 IQAMKU+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 FOZABN+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 SDWPYC+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 RGUFCP+CMSY10 Type 1 Builtin yes yes no 32 0 NJOMJZ+VnURWPalladioL Type 1 Custom yes yes no 36 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 54 0 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PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-08-03 02:25:18 CEST Size: 839069 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 297 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Method Development and Validation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Pharmacokinetics of Methylone, MDMA and Their Metabolites Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Chemicals and Materials Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Calibrators and Quality Control (QC) Solutions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Controlled Methylone and MDMA Administration to Humans Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Sample Preparation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Ultra-High-Performance Liquid Chromatography Tandem Mass Spectrometry (HPLC-MS/MS) Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Method Validation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Children: Item: Title: Linearity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Limit of Detection and Quantification Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Carryover Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Interferences Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Dilution Integrity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Stability Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Matrix Effect and Recovery Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Data Analysis and Statistics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Info: Title: Methylone and MDMA Pharmacokinetics Following Controlled Administration in Humans Author: Lourdes Poyatos, Alfredo Fabrizio Lo Faro, Diletta Berardinelli, Giorgia Sprega, Sara Malaca, Simona Pichini, Marilyn A. Huestis, Esther Papaseit, Clara Pérez-Mañá, Francesco Paolo Busardò and Magí Farré Subject: The aim of this study is to define, for the first time, human methylone and HMMC plasma pharmacokinetics following controlled administration of 50 200 mg methylone to 12 male volunteers. A new LC-MS/MS method was validated to quantify methylone, MDMA, and their metabolites in plasma. The study was a randomized, cross-over, double-blinded and placebo-controlled study, with a total of 468 plasma samples collected. First, 10 L of MDMA-d5, MDA-d5 and methylone-d3 internal standards were added to 100 L of plasma. Two mL of chloroform and ethyl acetate 9:1 (v/v) were then added, mixed well and centrifuged. The supernatant was fortified with 0.1 mL acidified methanol and evaporated under nitrogen. Samples were reconstituted with a mobile phase and injected into the LC-MS/MS instrument. The method was fully validated according to OSAC guidelines (USA). Methylone plasma concentrations increased in a dose-proportional manner, as demonstrated by the increasing maximum concentration (Cmax) and area under the curve of concentrations (AUC). Methylone Cmax values were reported as 153, 304, 355 and 604 ng/mL, AUC0 24 values were reported as 1042.8, 2441.2, 3524.4 and 5067.9 hng/mL and T1/2 values as 5.8, 6.4, 6.9 and 6.4 h following the 50, 100, 150 and 200 mg doses, respectively. Methylone exhibited rapid kinetics with a Tmax of 1.5 h for the 50 mg dose and 2 h approximately after all the other doses. HMMC exhibited faster kinetics compared to methylone, with a Cmax value that was 10 14-fold lower and an AUC0 24 value that was 21 29-fold lower. Methylone pharmacokinetics was linear across 50 200 mg oral doses in humans, unlike the previously described non-linear oral MDMA pharmacokinetics. An LC-MS/MS method for the quantification of methylone, MDMA and their metabolites in human plasma was achieved. Methylone exhibited linear pharmacokinetics in humans with oral doses of 50 200 mg. 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