WA2PilotMousePK.pdf

RFP/N01-CM-07014-39

Attachment 22, WA 2

NCI CONTRACT WORK ASSIGNMENT

Contractor: To be filled in WA Title: Analytical method development with provisional validation and pilot mouse PK/bioavailability studies with a small molecule to be determined

Contract No: N01-CM-________ WA No: 2 Modification No: 0 WA Originator: Project Officer Contracted WA Area:

Date Prepared: ________________

Part I. INITIATOR'S REQUEST

A. Period of Performance: __Month 1____thru __Month 2__ (2 months total)

B. WA Description:

Compound background summary would be provided here. Assume available information includes:

• Structure

• A measure of potency (e.g., NCI60 or other in vitro data)

• Any previously developed analytical methods (may be for neat compound only)

• Solubility and preliminary formulation information

• Dose ranges used in mouse xenograft studies (including route and schedule); single dose MTD not determined.

Specifically, the following tasks should be undertaken:

• Develop and perform preliminary validation of an LC-MS/MS method for the determination of the compound in mouse plasma. The method need not undergo full FDA/GLP validation, but rather should be shown to be accurate at a level suitable for early pharmacokinetic screening evaluations. Identification of a suitable internal standard is desirable.

• Perform pharmacokinetic studies in mice with i.v., i.p., and oral administration in the designated vehicle. These studies should be designed as pilot screening studies, with ≤ 10 timepoints and 3 mice per timepoint. Pilot studies to determine the appropriate timepoints may be proposed. Data analysis should include standard non-compartmental modeling to determine Cmax, Tmax, AUC, CL, t½, and bioavailability.

As indicated in Part II of this form, please provide an estimate of the cost and effort required for this work assignment, as well as a description of your approach to the studies to be performed.

C. WA Leader: Fill in PI name

D. Deliverables:

(1) Interim data

(1) Monthly status reports

RFP/N01-CM-07014-39

Attachment 22, WA 2

(2) Final WA report

E. Work Assignment Response Due Date: with proposal