8d27830e10fa44280512a53c952ad523 pmc_10254025.pdf 9a6f14063427cdcf81b13ca1e96346c6b024f708 pmc_10254025.pdf 2a552593aeb341f49a587df1413e49f8f59ea2ad23a66db49839db0ef42f44ac pmc_10254025.pdf Title: GC–MS/MS Determination of Synthetic Cathinones: 4-chloromethcathinone, N-ethyl Pentedrone, and N-ethyl Hexedrone in Oral Fluid and Sweat of Consumers under Controlled Administration: Pilot Study Subject: This study presents a validated GC-MS/MS method for the detection and quantification of 4-chloromethcathinone or clephedrone (4-CMC), N-ethyl Pentedrone (NEP), and N-ethyl Hexedrone (NEH, also named HEXEN) in oral fluid and sweat and verifies its feasibility in determining human oral fluid concentrations and pharmacokinetics following the administration of 100 mg of 4-CMC orally and 30 mg of NEP and NEH intranasally. A total of 48 oral fluid and 12 sweat samples were collected from six consumers. After the addition of 5 L of methylone-d3 and 200 L of 0.5 M ammonium hydrogen carbonate, an L/L extraction was carried out using ethyl acetate. The samples, dried under a nitrogen flow, were then derivatized with pentafluoropropionic anhydride and dried again. One microliter of the sample reconstituted in 50 L of ethyl acetate was injected into GC-MS/MS. The method was fully validated according to international guidelines. Our results showed how, in oral fluid, the two cathinones taken intranasally were absorbed very rapidly, within the first hour, when compared with the 4-CMC which reached its maximum concentration peak in the first three hours. We observed that these cathinones were excreted in sweat in an amount equivalent to approximately 0.3% of the administered dose for 4-CMC and NEP. The total NEH excreted in sweat 4 h after administration was approximately 0.2% of the administered dose. Our results provide, for the first time, preliminary information about the disposition of these synthetic cathinones in the consumers’ oral fluid and sweat after controlled administration. Keywords: synthetic cathinones; gas-chromatography tandem mass spectrometry; oral fluid pharmacokinetics; sweat; 4-chloromethcathinone; N-ethyl pentedrone; N-ethyl hexedrone Author: Melani Nuñez-Montero, Claudia Lombroni, Nunzia La Maida, Maria Concetta Rotolo, Simona Pichini, Esther Papaseit, Olga Hladun, Mireia Ventura, Lourdes Poyatos, Clara Pérez-Mañá, Magí Farré and Emilia Marchei Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat May 27 16:44:16 2023 CEST ModDate: Sat May 27 16:45:47 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1975966 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- IOJCNK+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 AMRDEP+VnURWPalladioL Type 1 Custom yes yes no 15 0 ONJNCB+EURM10 Type 1 Builtin yes 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yes yes no 216 0 EDOICM+PalatinoLinotype TrueType MacRoman yes yes no 219 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-09-21 02:29:00 CEST RepresentationInformation: pmc_10254025.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-09-16 02:17:21 CEST Size: 1975966 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 373 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Method Development and Validation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Pharmacokinetics of 4-CMC, NEP, and NEH in Oral Fluid Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: 4-CMC, NEP, and NEH in Sweat Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Children: Item: Title: Chemicals and Materials Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Calibrators and Quality Control (QC) Solutions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Participants Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Design, Treatments and Collection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Sample Preparation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: GC-MS/MS Conditions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Method Validation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Pharmacokinetic Parameters 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: GC MS/MS Determination of Synthetic Cathinones: 4-chloromethcathinone, N-ethyl Pentedrone, and N-ethyl Hexedrone in Oral Fluid and Sweat of Consumers under Controlled Administration: Pilot Study Author: Melani Nuñez-Montero, Claudia Lombroni, Nunzia La Maida, Maria Concetta Rotolo, Simona Pichini, Esther Papaseit, Olga Hladun, Mireia Ventura, Lourdes Poyatos, Clara Pérez-Mañá, Magí Farré and Emilia Marchei Subject: This study presents a validated GC-MS/MS method for the detection and quantification of 4-chloromethcathinone or clephedrone (4-CMC), N-ethyl Pentedrone (NEP), and N-ethyl Hexedrone (NEH, also named HEXEN) in oral fluid and sweat and verifies its feasibility in determining human oral fluid concentrations and pharmacokinetics following the administration of 100 mg of 4-CMC orally and 30 mg of NEP and NEH intranasally. A total of 48 oral fluid and 12 sweat samples were collected from six consumers. After the addition of 5 L of methylone-d3 and 200 L of 0.5 M ammonium hydrogen carbonate, an L/L extraction was carried out using ethyl acetate. The samples, dried under a nitrogen flow, were then derivatized with pentafluoropropionic anhydride and dried again. One microliter of the sample reconstituted in 50 L of ethyl acetate was injected into GC-MS/MS. The method was fully validated according to international guidelines. Our results showed how, in oral fluid, the two cathinones taken intranasally were absorbed very rapidly, within the first hour, when compared with the 4-CMC which reached its maximum concentration peak in the first three hours. We observed that these cathinones were excreted in sweat in an amount equivalent to approximately 0.3% of the administered dose for 4-CMC and NEP. The total NEH excreted in sweat 4 h after administration was approximately 0.2% of the administered dose. Our results provide, for the first time, preliminary information about the disposition of these synthetic cathinones in the consumers’ oral fluid and sweat after controlled administration. Keywords: synthetic cathinones; gas-chromatography tandem mass spectrometry; oral fluid pharmacokinetics; sweat; 4-chloromethcathinone; N-ethyl pentedrone; N-ethyl hexedrone Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat May 27 16:44:16 CEST 2023 ModDate: Sat May 27 16:45:47 CEST 2023 ID: 0x4ce6a670c63db81b64f8851dc39231f0, 0x4ce6a670c63db81b64f8851dc39231f0 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: XBORAL+URWPalladioL-Ital FontSubset: true FirstChar: 40 LastChar: 121 FontDescriptor: FontName: XBORAL+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: UPQIVM+URWPalladioL-BoldItal FontSubset: true FirstChar: 109 LastChar: 122 FontDescriptor: FontName: UPQIVM+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ONJNCB+EURM10 FontSubset: true FirstChar: 11 LastChar: 27 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