Mycophenolic acid

Dissociation constant

Administrative data

Endpoint:

dissociation constant

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted under recognised test methods

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

This protocol follows closely the recommendations made in the Environmental Assessment Technical Assistance Handbook (Food and Drug Administration, March 1987) and in The Determination of Ionization Constants (Albert, A. and Serjeant, E.P., 1984).

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Mycophenolic acid

EC Number:

246-119-3

EC Name:

Mycophenolic acid

Cas Number:

24280-93-1

Molecular formula:

C17H20O6

IUPAC Name:

6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid

Details on test material:

Molecular formula: C17H20O6
CAS registry number: 24280-93-1
Solubility, mg/mL
- pH 5: 0.03
- pH 7: 4.0

Results and discussion

Dissociating properties:

yes

Dissociation constant

No.:

#2

pKa:

>= 8.04 - <= 8.05

Temp.:

22.5 °C

Any other information on results incl. tables

Absorbance and pH raw data for each of the three determinations. The data was used to construct plots of pH versus absorbance. Each of the plots indicated a single, significant drop in absorbance, with an inflection point occurring at a pH of about 8. Further processing of the data according to procedures already described resulted in plots of pH versus the negative logarithm of [HA]/[A']. Linear regression of the plots resulted in the following results. For Determination 1, the value of the pKa, as the x-intercept (y=O) was 8.039. For Determinations 2and 3, the corresponding values were 8.050 and 8.045. The value of the pKa of mycophenolic acid, at an ionic strength of µ = 0.1 and an average temperature of 22.5 +0.5^OC, was determined in this experiment to be 8.045.

Applicant's summary and conclusion

Conclusions:

The average pKa, of the phenolic group of mycophenolic acid at 22.5 oC was found to be 8.045 or Ka= 9.016 x 10-9M.

Executive summary:

Purpose. This study was conducted to determine the value of the second dissociation constant of mycophenolic acid in the pH range from 5 to 9.

 

Performance. This study was conducted in triplicate using the spectrophotometric method. A 1.99 x 10^-2mg/mL mycophenolic acid solution was prepared in 0.1M KCl (µ=0.1). The solution was then titrated using 0.1N KOH from a pH of about 5 to a pH of about 11. Samples were withdrawn for a determination of absorbance at 341nm after each addition of titrant. The pH was determined for each sample. The degree of ionization of mycophenolic acid at each pH value was calculated from the absorbance data. The data was then used to determine the dissociation constant.

 

Results. The average pK_a, of the phenolic group of mycophenolic acid at22.5^oCwas found to be8.045or K_a=9.016x10^-9M.