Sodium 2-hydroxyethanesulphonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Remarks:

Parallel Artificial Membrane Permeation Assay (PAMPA)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2022-2023

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2023

Report date:

2023

Materials and methods

Objective of study:

other: Passive permeation

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The passive permeation of SI was assessed in the Parallel Artificial Membrane Permeation Assay (PAMPA; Kansy et al. (1998) J. Med. Chem. 41, 1007).
Permeation experiments were carried out in a Multiscreen 96 well tray (donor) covered by a 96-well Multiscreen Immobilon (acceptor). The donor plate was filled with test compounds and reference compounds. Three refence compounds were included (Ceftriaxone, Guanabenz, Carbamazepine), each known for their low, medium and high permeability, respectively. The transport study was initiated by applying 150 µL PBS-buffer to the acceptor plate. After 15 – 16 h of diffusion at room temperature, the contents of the acceptor and donor plate were collected and quantified using LC-MS detection. The permeability of SI was expressed as flux% and recovery%.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 2-hydroxyethanesulphonate

EC Number:

216-343-6

EC Name:

Sodium 2-hydroxyethanesulphonate

Cas Number:

1562-00-1

Molecular formula:

C2H6O4S.Na

IUPAC Name:

sodium 1,4-bis[(2-ethylhexyl)oxy]-1,4-dioxobutane-2-sulfonate

Test material form:

other: Powder

Details on test material:

Storage: at room temperature

Results and discussion

Main ADME results

Main ADME results 1

Type:

other: Flux % (with lipid layer)

Results:

0%

Main ADME results 2

Type:

other: Flux % (without lipid layer)

Results:

107.8%

Main ADME results 3

Type:

other: Mean Recovery % (with lipid layer)

Results:

97.2%

Main ADME results 4

Type:

other: Mean Recovery % (without lipid layer)

Results:

131.1%

Toxicokinetic / pharmacokinetic studies

Details on absorption:

For SI, no permeability across lipophilic lecithin membranes was observed (0% flux).

Recoveries, i.e. the sum of test item recovered from the donor and acceptor compartment were high in presence (97.2%) or absence (131.1%) of lipid layer. Furthermore, free flux of SI through the plates without lipid layer was observed. Therefore, unspecific binding properties of SI towards the test materials / filter device or chemical instability is unlikely and SI can be classified according to the pre-defined classification scheme as low permeable.

Recovery values for internal controls ceftriaxone, guanabenz and carbamazepin were high (=102%) and permeabilities of reference items were classified according to the pre-defined classification scheme (ceftriaxone showed a low permeation with 0.02% flux, guanabenz a medium permeation with 53% flux and carbamazepine a high flux rate of 106%).

The validity of the experiment was confirmed by a post experimental membrane integrity test (Lucifer yellow permeation), which evidenced the integrity of the filter membrane and lipid layer (i.e. flux rates < 5%).

Any other information on results incl. tables

Table 4 - PAMPA permeation of test and reference items (n=3)

Test / reference items	condition	Flux %	SD	%CV	Mean Recovery %	SD	Comments
SI	With lipid layer	0.0	0.0	n.a.	97.2	8.3	Low permeable
	Without lipid layer	107.8	16.0	14.9	131.1	20.7	Control
Ceftriaxone	With lipid layer	0.02	0.02	89.6	102.1	6.2	Low permeable reference
Guanabenz		53.3	3.7	7.0	176.0	7.1	Medium-high permeable reference
Carbamazepine		105.7	7.4	7.0	148.5	11.2	High permeable, reference accepted

 

Applicant's summary and conclusion

Conclusions:

Based on the results of a parallel artificial membrane permeation assay, the flux of SI was concluded to be 0%. This indicates that SI is not able to passively permeate a lipid layer, and it can therefore be considered as a low permeable compound.