d679b171f274b276d40bdf31cd78ee5e pmc_10143603.pdf 97f71dbc89d76e6eabdfeddee6f2c0b000fc9f0f pmc_10143603.pdf b4ed63dd5e655f8c06ea8e6eb6f16a33eed3f898bf3718020b1c7de6d67e8e78 pmc_10143603.pdf Title: Usefulness of Oral Fluid for Measurement of Methylone and Its Metabolites: Correlation with Plasma Drug Concentrationsand the Effect of Oral Fluid pH Subject: The aim of this study was to investigate methylone and its metabolites concentration in oral fluid following controlled increasing doses, focusing on the effect of oral fluid pH. Samples were obtained from a clinical trial where twelve healthy volunteers participated after ingestion of 50, 100, 150 and 200 mg of methylone. Concentration of methylone and its metabolites 4-hydroxy-3-methoxy-N-methylcathinone (HMMC) and 3,4-methylenedioxycathinone in oral fluid were measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Pharmacokinetic parameters were estimated, and the oral fluid-to-plasma ratio (OF/P) at each time interval was calculated and correlated with the oral fluid pH using data from our previous study in plasma. Methylone was detected at all time intervals after each dose; MDC and HMMC were not detectable after the lowest dose. Oral fluid concentrations of methylone ranged between 88.3–503.8, 85.5–5002.3, 182.8–13,201.8 and 214.6–22,684.6 ng/mL following 50, 100, 150 and 200 mg doses, respectively, peaked between 1.5 and 2.0 h, and were followed by a progressive decrease. Oral fluid pH was demonstrated to be affected by methylone administration. Oral fluid is a valid alternative to plasma for methylone determination for clinical and toxicological studies, allowing for a simple, easy and non-invasive sample collection. Keywords: methylone; oral fluid; pharmacokinetics; humans; LC–MS/MS Author: Giorgia Sprega, Alessandro Di Giorgi, Lourdes Poyatos, Esther Papaseit, Clara Pérez-Mañá, Anastasio Tini, Simona Pichini, Francesco Paolo Busardò, Alfredo Fabrizio Lo Faro and Magí Farré Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Mar 24 07:58:08 2023 CET ModDate: Fri Mar 24 08:02:33 2023 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1538320 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 SGUCNA+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 WECUOA+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 LYLGVP+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 KORLVE+VnURWPalladioL Type 1 Custom yes yes no 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yes 158 0 PIIPGH+PalatinoLinotype TrueType WinAnsi yes yes no 164 0 PIIPGJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 167 0 PIJAAH+PalatinoLinotype TrueType MacRoman yes yes no 170 0 PIJAFH+Arial CID TrueType Identity-H yes yes yes 173 0 PIIPGF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 184 0 PIIPGG+PalatinoLinotype CID TrueType Identity-H yes yes yes 187 0 PIIPGH+PalatinoLinotype TrueType WinAnsi yes yes no 193 0 PIIPGJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 196 0 PIJAAH+PalatinoLinotype TrueType MacRoman yes yes no 199 0 PIJAFH+Arial CID TrueType Identity-H yes yes yes 202 0 PIIPGF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 216 0 PIIPGG+PalatinoLinotype CID TrueType Identity-H yes yes yes 219 0 PIIPGH+PalatinoLinotype TrueType WinAnsi yes yes no 225 0 PIIPGJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 228 0 PIJAAH+PalatinoLinotype TrueType MacRoman yes yes no 231 0 PIJAFH+Arial CID TrueType Identity-H yes yes yes 234 0 PIIPGF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 245 0 PIIPGG+PalatinoLinotype CID TrueType Identity-H yes yes yes 248 0 PIIPGH+PalatinoLinotype TrueType WinAnsi yes yes no 254 0 PIIPGJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 257 0 PIJAAH+PalatinoLinotype TrueType MacRoman yes yes no 260 0 PIJAFH+Arial CID TrueType Identity-H yes yes yes 263 0 PIIPGF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 277 0 PIIPGG+PalatinoLinotype CID TrueType Identity-H yes yes yes 280 0 PIIPGH+PalatinoLinotype TrueType WinAnsi yes yes no 286 0 PIIPGJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 289 0 PIJAAH+PalatinoLinotype TrueType MacRoman yes yes no 292 0 PIJAFH+Arial CID TrueType Identity-H yes yes yes 295 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-08-08 02:25:20 CEST RepresentationInformation: pmc_10143603.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-08-01 02:31:27 CEST Size: 1538320 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 446 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: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Subjects and Study Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Chemicals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Oral Fluid Samples Collection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Sample Preparation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: pH Measurements of Oral Fluid Samples Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Pharmacokinetics and Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Children: Item: Title: Concentration Time Profile and Pharmacokinetic of Methylone, MDC and HMMC in Oral Fluid Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Measurement of pH in Oral Fluid Samples Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: OF/plasma Ratio for Methylone Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Info: Title: Usefulness of Oral Fluid for Measurement of Methylone and Its Metabolites: Correlation with Plasma Drug Concentrationsand the Effect of Oral Fluid pH Author: Giorgia Sprega, Alessandro Di Giorgi, Lourdes Poyatos, Esther Papaseit, Clara Pérez-Mañá, Anastasio Tini, Simona Pichini, Francesco Paolo Busardò, Alfredo Fabrizio Lo Faro and Magí Farré Subject: The aim of this study was to investigate methylone and its metabolites concentration in oral fluid following controlled increasing doses, focusing on the effect of oral fluid pH. Samples were obtained from a clinical trial where twelve healthy volunteers participated after ingestion of 50, 100, 150 and 200 mg of methylone. Concentration of methylone and its metabolites 4-hydroxy-3-methoxy-N-methylcathinone (HMMC) and 3,4-methylenedioxycathinone in oral fluid were measured using liquid chromatography tandem mass spectrometry (LC MS/MS). Pharmacokinetic parameters were estimated, and the oral fluid-to-plasma ratio (OF/P) at each time interval was calculated and correlated with the oral fluid pH using data from our previous study in plasma. Methylone was detected at all time intervals after each dose; MDC and HMMC were not detectable after the lowest dose. Oral fluid concentrations of methylone ranged between 88.3 503.8, 85.5 5002.3, 182.8 13,201.8 and 214.6 22,684.6 ng/mL following 50, 100, 150 and 200 mg doses, respectively, peaked between 1.5 and 2.0 h, and were followed by a progressive decrease. Oral fluid pH was demonstrated to be affected by methylone administration. Oral fluid is a valid alternative to plasma for methylone determination for clinical and toxicological studies, allowing for a simple, easy and non-invasive sample collection. 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