1-methylpiperidine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication which meets basic scientific principles.

Data source

Reference

Reference Type:

publication

Title:

Biological N-oxidation of piperidine in vitro

Author:

Wang DY, Gorrod JW, Beckett AH

Year:

1989

Bibliographic source:

Acta Pharmacol. Sin. 10, 252-256 (1989)

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

In the study the biological N-oxidation of piperidine was investigated in vitro. After incubation of piperidine-HCl in a fortified rat liver microsomal preparation (9000 x g supernatant) at 37°C for 30 min, metabolites were analysed by Thin-layer chromatography (TLC), Gas-liquid chromatography (GLC) HPLC, Gas chromatography (GC)-MS and MS.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Piperidinium chloride

EC Number:

228-033-8

EC Name:

Piperidinium chloride

Cas Number:

6091-44-7

IUPAC Name:

piperidinium chloride

Details on test material:

- Name of test material (as cited in study report): Pip-HCL

Radiolabelling:

no

Administration / exposure

Details on exposure:

VEHICLE
- Concentration in vehicle: 10 µmol Pip-HCl/mL water

Duration and frequency of treatment / exposure:

30 min

Doses / concentrations

Remarks:

Doses / Concentrations:
0.121 mg/mL

Details on study design:

INCUBATION
- Incubation of a microsomal preparation of the liver of male albino Wistar rats (9000 x g supernatant fractions) together with the test substance (0.5 mL of the substrate solution) was carried out in a volume of 3.5 mL at 37°C for 30 min using a shaking water bath.

Details on dosing and sampling:

METABOLITE CHARACTERISATION STUDIES
- Extraction of metabolites: After incubation, a two step extraction of metabolites was performed using NaCl and chloroform. The chloroform extract was evaporated at 42 °C under nitrogen. The residue was dissolved in methanol. Controls and blanks were treated in the same manner.
- Time of sampling: After 30 minutes incubation
- Method type(s) for identification:
• Thin-layer chromatography (TLC) was carried out on precoated silica gel; As solvents, methanol and a chloroform, methanol and acetic acid mixture were used. Primary and secondary amines were also detected by converting to dinitrophenyl (DNP) derivatives. DNP derivatives were extracted with cyclohexane.
• Gas-liquid chromatography (GLC)
• High performance liquid chromatography (HPLC) ,
• Gas chromatography (GC)-MS
• Mass spectrometry (MS).

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Piperidine hydrochloride was oxidized in a fortified rat liver microsomal preparation to N-hydroxy piperidine (N-OH-Pip) and 2,3,4,5-tetrahydropyridine-1-oxide (THPO):
After chloroform extraction, TLC and subsequent exposure to Iodide (I₂) vapour two new metabolites were detected. The products have Rf (retardation factor) values close to those of authentic N-OH-Pip and THPO. After GLC, GC-MS, HPLC and TLC both metabolites were identified.
Other known metabolites are 3-hydroxy piperidine, 4-hydroxy piperidine and Piperidone-2.

Piperidine is N-oxidized to the corresponding N-Hydroxylamine.