Tricyclo[3.3.1.13,7]decane-1-acetic acid, .alpha.-[[(1,1-dimethylethoxy)carbonyl]amino]-3-hydroxy-, (.alpha.S)-

Vapour pressure

Administrative data

Endpoint:

vapour pressure

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31 December 2004 to 23 May 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was conducted in 2005 according to EU and OECD Method and in accordance with GLP. The study material is well characterized.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 104 (Vapour Pressure Curve)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method A.4 (Vapour Pressure)

Deviations:

no

GLP compliance:

yes

Type of method:

effusion method: by loss of weight or by trapping vaporisate

Remarks:

modified Knudsen Effusion apparatus

Test material

Test material information

Constituent 1

Reference substance name:

(2S)-2-{[(tert-butoxy)carbonyl]amino}-2-(3-hydroxyadamantan-1-yl)acetic acid

EC Number:

700-361-0

Cas Number:

361442-00-4

Molecular formula:

C17H27NO5

IUPAC Name:

(2S)-2-{[(tert-butoxy)carbonyl]amino}-2-(3-hydroxyadamantan-1-yl)acetic acid

Constituent 2

Reference substance name:

1-Hydroxyadamantanyl-3-(S)-Boc-glycine

IUPAC Name:

1-Hydroxyadamantanyl-3-(S)-Boc-glycine

Details on test material:

Off-white powder; stored at room temperature; received at testing laboratory on 06-10-2004.

Results and discussion

Vapour pressure

Remarks on result:

other: too low to be determined by this method-the theoretical lower detection limit of the Knudsen Effusion apparatus is 1 x 10-4 Pa.

Transition / decomposition

Transition / decomposition:

no

Any other information on results incl. tables

Examination of the DSC thermograms indicated that a maximum test temperature of 170°C would be practical in the vapour pressure tests in order to ensure that the samples remained solid.

Preliminary tests showed that no significant weight changes were evident, or that the calculated results were consistent. the following "definitive" testing was performed. After 140 minutes at 170°C, a small weight loss was recorded, most likely due to the

evaporation of associated volatile impurities. However, when the samples continued to be held isothermally at 170°C, no further significant weight losses were recorded. The weight losses were too small to determine a value for the vapour pressure. The theoretical lower detection limit of the Knudsen Effusion apparatus is 1 x 10-4 Pa.

 Weight Changes during the Vapour Pressure Test for BMS 528233-01

Run number	Date	Time	Temperature (°C)	Test 5 mass (mg)	Test 6 mass (mg)
1*	19/5/05	11:10	170	53.540	54.675
	19/5/05	13:30	170	53.533	54.657
2	19/5/05	13:35	170	53.533	54.657
	20/5/05	08:43	170	53.535	54.659
3	20/5/05	08:48	170	53.535	54.659
	23/5/05	08:45	170	53.534	54.658

* - Initial loss of mass is most likely due to loss of associated volatile

A sample was subjected to DSC analysis on completion of the test, to determine if any physical change had occurred during the test. The DSC thermogram showed no significant changes to the thermograms produced in the melting and boiling point determinations, suggesting no physical change had occurred.

Applicant's summary and conclusion

Conclusions:

The vapour pressure of BMS 528233-01 was too low to be accurately determined by the Knudsen Effusion apparatus. There was no significant weight loss from the test substance at 170°C, the maximum temperature that could be used in the test. The theoretical lower detection limit of the Knudsen Effusion apparatus is 1 x 10-4 Pa.

Executive summary:

The vapour pressure of BMS 528233-01 was too low to be accurately determined by the Knudsen Effusion apparatus. There was no significant weight loss from the test substance at 170°C, the maximum temperature that could be used in the test. The theoretical lower detection limit of the Knudsen Effusion apparatus is 1 x 10-4 Pa.