Determination of GI147211 in human blood by HPLC with fluorescence detection.
GI147211 (GG211) is a camptothecin analogue, which exhibits antileukemic and antitumor activity by blocking DNA synthesis. The drug stability considerations and specimen handling were important aspects in method development and validation. This method involves collection of blood at the clinical site, immediate freezing, and storage at -70 degrees C. The lactone form is extracted from blood at physiological pH with a mixture of n-butyl chloride and acetonitrile (4:1); the carboxylate is not extracted under these conditions. After evaporation the extract is injected into an HPLC system with a fluorescence detector set at 378/420 nm. The internal standard used is 6,7-dimethoxy-4-methylcoumarin. The main advantages of the procedure are the separation of lactone and carboxylate by means of extraction, simplified specimen collection at clinical sites and the ability to inject almost all of the extracted material (extraction recovery, 60%) into an HPLC system. The method has been validated over the range 0.15-100 ng ml-1 with sufficient precision and accuracy (coefficient of variation below 10%) to support pharmacokinetic studies. Under the conditions of this procedure, the drug is stable in human blood at -70 degrees C for at least 93 days, as well as through two additional freeze-thaw cycles.
Selinger
K
K
Glaxo Inc. Research Institute, Research Triangle Park, NC 27709, USA.
Smith
G
G
Depee
S
S
Aureche
C
C
D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics; D001711:Biotransformation; D002138:Calibration; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D007262:Infusions, Intravenous; D009369:Neoplasms / Q000378:metabolism; D012015:Reference Standards; D013050:Spectrometry, Fluorescence
D000970:Antineoplastic Agents; C091719:lurtotecan; D002166:Camptothecin