Two Hofmann-Martius-like rearrangement products generated in the production of duloxetine hydrochloride were studied. The structures and generation mechanism of the two Hofmann-Martius rearrangement products were analyzed by LC-MS and NMR. The results showed that under the acidic conditions, the naphthol ether bond of duloxetine would break down and the intermediates of naphthol and the alkyl thiophene cation was generated; the two Hofmann-Martius-like rearrangement products were proven to be a pair of isomers produced by nucleophilic substitution between the naphthol intermediate state and the alkyl thiophene cation intermediate state at the ortho or the para position, respectively. The production of two isomers was related to the strong acidic and protic solvent environment. Therefore, in the salting process of duloxetine hydrochloride, the pH value should be controlled in the range of 3-7 and temperature should be maintained below 50 °C, as well as the nonprotic solvent acetone is chosen to avoid generation of the two isomers.

OBJECTIVEThe purpose of the report was to investigate the causes of CSF leakage and discuss the methods for prevention and management of CSF leakage following translabyrinthine resection of acoustic neuromas.

METHODSA retrospective review of cerebrospinal fluid leakage following translabyrinthine approach for 152 acoustic neuromas patients, from January 1983 to December 2013, was performed. The cases were divided into two groups, traditional and modified closure techniques. The incidence of CSF leakage was compared between the two groups.

RESULTSThe incidence of postoperative CSF leakage by translabyrinthine approach was 5.9% (9/152), with four cases of rhinorrhea, two case of wound leakage, one case of rhinorrhea and otorrhea, one case of otorrhea, and one case of rhinorrhea and wound leakage. The CSF leakage incidence of traditional closure technique was 14.3% (5/35); the incidence of modified closure technique was 3.4% (4/117). After introducing a modified closure technique, the incidence of the CSF leakage significantly decreased.

CONCLUSIONSAs a common complication of translabyrinthine approach, the incidence of CSF leakage is closely related to the closure technique. The incidence of the CSF leakage should decrease dramatically when adopting the modified closure technique.

Adult ; Cerebrospinal Fluid Leak ; prevention & control ; Craniotomy ; Ear, Inner ; surgery ; Female ; Humans ; Male ; Middle Aged ; Neuroma, Acoustic ; surgery ; Otologic Surgical Procedures ; adverse effects ; methods ; Postoperative Complications ; prevention & control ; Retrospective Studies