Validation study of assay method for DX‐8951 and its metabolite in human plasma and urine by high‐performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry

Abstract

A new liquid chromatographic/mass spectrometric assay has been developed for the determination of DX-8951, a new anti-tumor drug, and its 4-hydroxymethyl metabolite (UM-1) in human plasma and urine. Solid-phase extractions were used for sample preparation. A gradient reverse-phase HPLC separation was developed with mobile phases consisting of trifluoroacetic acid and methanol. The detection was conducted using atmospheric pressure chemical ionization tandem mass spectrometry in the selected reaction monitoring mode. A structural analog, camptothecin (CPT), was used as the internal standard. The assay was validated for the determination of DX-8951 and UM-1 in human plasma and urine. The lower limits of quantitation of DX-8951 and UM-1 were 0.1 ng/mL in plasma and 1 ng/mL in urine. The method showed a satisfactory sensitivity, precision, accuracy, recovery and selectivity.

Validation study of a method for assaying DE-310, a macromolecular carrier conjugate containing an anti-tumor camptothecin derivative, and the free drug in tumor tissue by high performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry

“…It is thought that the sensitivity of HPLC is not adequate to analyze tissue samples, and the total analysis time is relatively long. Furthermore, we have developed an LC/MS/MS method for the determination of DX-8951 in human plasma (Oguma et al, 2001b). It is suggested that the use of this LC/ MS/MS method enables the chromatographic run time to be reduced, and is applicable for analyzing both released free drugs and conjugated drug in tumor tissue.…”

A phase II clinical and pharmacokinetic study of intravenous exatecan mesylate (DX-8951f) in patients with untreated metastatic gastric cancer

“…Plasma samples were analyzed at MDS Pharma Services (Montreal, Canada). Total DX-8951 plasma concentrations were quantified using a validated high-performance liquid chromatography method [17,18]. The lower limit of quantitation was 0.201 ng/mL.…”

Quantitative determination of DRF‐1042 in human plasma by HPLC: validation and application in clinical pharmacokinetics

“…There are several liquid-liquid extraction approaches available for simultaneous measurement of the δ-lactone and δ-hydroxy acid forms of various CPTs in human plasma (Beijnen et al, 1993;Li and Zhang, 1996;Warner and Burke, 1997;Loos et al, 1997;Sparreboom et al, 1998a;Sai et al, 2002). Solid phase extraction (Barilero et al, 1992;Takimoto et al, 1994;Oguma et al, 2000Oguma et al, , 2001 and restricted access media methodologies have been recently reported (Ma et al, 2002) for simultaneous determination of these CPT forms in human plasma. All of these methods require immediate sample processing in order to avoid inter-conversion between the two forms.…”