Sensitive determination of irinotecan (CPT-11) and its active metabolite SN-38 in human serum using liquid chromatography-electrospray mass spectrometry.
A couple of sensitive and accurate liquid chromatography-electrospray mass spectrometry (LC- S-MS) methods for the determination of the total forms of irinotecan and its active metabolite SN-38 in human serum, using the same chromatographic and detection conditions, is presented. Both used camptothecin as internal standard (I.S.). The sample pretreatment for irinotecan involved a simple protein precipitation with acetonitrile, whereas a liquid-liquid extraction was necessary for SN-38. A Symmetry C18, 3.5 microm (150 x 1 mm I.D.) reversed-phase column was used for the chromatographic separation, together with a gradient elution of acetonitrile in 5 mM ammonium formate buffer (pH 3) as mobile phase. After ionisation in the pneumatically-assisted electrospray source and in-source collision induced dissociation, acquisition was performed in the selected ion monitoring mode. Recoveries were 69 and 47% on average, detection limits 2.5 and 0.25 ng/ml and quantitation limits 10 and 0.5 ng/ml for irinotecan and SN-38, respectively. Reproducibility was good and the method was linear from limits of quantitation up to 10,000 ng/ml for irinotecan, and up to 100 ng/ml for SN-38. This sensitive and highly specific method is suitable both for pharmacokinetic studies and routine therapeutic drug monitoring.
Ragot
S
S
Department of Pharmacology and Toxicology, University Hospital, Limoges, France.
Marquet
P
P
Lachâtre
F
F
Rousseau
A
A
Lacassie
E
E
Gaulier
J M
JM
Dupuy
J L
JL
Lachâtre
G
G
D000097:Acetonitriles; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000097:Acetonitriles; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin; C032159:acetonitrile