title: Modifications and insights into a method for the analysis of the nitrogen mustard mechlorethamine by high-performance liquid chromatography.
abstract: Previously, a method was presented for the analysis of mechlorethamine by derivatization of this unstable nitrogen mustard to bis(2-phenylthioethyl)methylamine (PTEMA), a stable compound suitable for analysis by HPLC with UV detection [J.C. Reepmeyer, J. Chromatogr. A, 1085 (2005) 262]. Mechlorethamine HCl served as a reference standard and it was derivatized in situ simultaneously with samples of mechlorethamine HCl in ointment preparations. This paper presents the synthesis of PTEMA on a gram scale, synthesis of its picrate salt, bis(2-phenylthioethyl)methylamine picrate (PTEMAP), and isolation of the picrate as a crystalline solid. PTEMAP may serve as a reference standard replacing the toxic mechlorethamine HCl. Insights into the handling, storage, drying, and hygroscopic properties of mechlorethamine HCl and PTEMAP are discussed. In addition, one step following the derivatization procedure in the original method is recognized as a potential for error, and a procedure relating to the order of addition of reagents is presented to avoid this error. The method has been extended to the analysis of mechlorethamine in aqueous solutions.
authors.affiliation: United States Food and Drug Administration, Center for Drug Evaluation and Research, Office of Phamaceutical Science, Division of Pharmaceutical Analysis, FDA, 1114 Market Street, Room 1002, St. Louis, MO 63101, USA. john.reepmeyer@fda.hhs.gov
authors.forename: John C
authors.initials: JC
authors.lastname: Reepmeyer
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Ritschel
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards; D004048:Diethylamines / Q000032:analysis* / Q000138:chemical synthesis; D008466:Mechlorethamine / Q000032:analysis* / Q000592:standards; D015394:Molecular Structure; D012680:Sensitivity and Specificity; D012996:Solutions / Q000737:chemistry; D013440:Sulfides / Q000032:analysis* / Q000138:chemical synthesis; D014867:Water / Q000737:chemistry
chemical_list: D004048:Diethylamines; D012996:Solutions; D013440:Sulfides; C529885:bis(2-phenylthioethyl)methylamine; D014867:Water; D008466:Mechlorethamine