A liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of actinomycin-D and vincristine in children with cancer

Abstract

Actinomycin-D (Act-D) and vincristine (VCR) are cytotoxic agents commonly used in the treatment of pediatric cancers. To date, there are few published methods on quantifying Act-D or VCR and no published methods on quantifying the two drugs together. We present a methodology for the simultaneous quantification of Act-D and VCR in human plasma using liquid chromatography-tandem mass spectrometry (LC/MS/MS) detection. Following solid phase extraction, plasma samples were separated and analyzed using electrospray ionization (ESI). The lower limit of quantitation (LLOQ) for both Act-D and VCR was 0.5 ng/ml. The analytical accuracy for detection of both Act-D and VCR was > or = 90%. The analytical precision, as estimated by the coefficient of variation was < or = 6% for Act-D and < or = 11% for VCR. Given the prevalence of the use of the two drugs as combination therapy in a variety of pediatric oncological indications, the small sample volume requirements and the assay sensitivity, this methodology is expected to support several ongoing and future pediatric trials.

An LC‐MS/MS method for simultaneous determination of vincristine and verapamil in rat plasma after oral administration of a dual agent formulation

“…For the determination of vincristine in plasma, radioimmunoassay (Nelson, 1982), HPLC (Koopmans et al, 2001;Embree et al, 1997;Bloemhof et al, 1991) and liquid chromatographicmass spectrometric methods (Dennison et al, 2008;Lee et al, 2007;Skolnik et al, 2006;Corona et al, 2008;Guilhaumou et al, 2010) have been reported. Some of these methods used a large volume of plasma sample (0.3-4 mL) or needed longer chromatographic run time (8 min), while others employed complicated extraction processes (on-line extraction step after precipitation).…”

Antineoplastic drugs and their analysis: a state of the art review

“…354,355 For the same compound, a ten-fold increase in sensitivity was observed in LC-MS. 361 Due to the concomitant administration of vincristine and actinomycin D in the treatment of various pediatric cancers, several LC-MS methods have been developed for the simultaneous determination of these two anticancer drugs in biological matrices. [356][357][358][359] An LOD of 0.007 ng mL −1 and LOQ of 0.05 ng mL −1 were reached for the analysis of actinomycin D in plasma using a SPE-LC-MS procedure. 358 A CE method coupled to chemiluminescence detection was also reported for the determination of mitoxantrone in injectable solutions and biological samples.…”

“…LC was generally used for the determination of mitoxanthrone and actinomycin D. Developed methods were based on C18 stationary phase, coupled to UV 354,355 and MS detection. [356][357][358][359][360][361] An LOQ of 5 ng mL −1 was obtained for the LC-UV analysis of mitoxantrone in plasma. 354,355 For the same compound, a ten-fold increase in sensitivity was observed in LC-MS. 361 Due to the concomitant administration of vincristine and actinomycin D in the treatment of various pediatric cancers, several LC-MS methods have been developed for the simultaneous determination of these two anticancer drugs in biological matrices.…”

“…The analysis of vinca alkaloids has been carried out on plant extracts, [398][399][400][401][402][403] pharmaceutical formulations, 316,404 biological samples 358,359,[405][406][407][408][409][410][411][412][413][414][415][416][417][418][419][420]421 and environmental samples. 18,19,134,307,422 Vinca alcaloid extraction from plants was generally performed by ultrasound in acid media followed by LLE.…”

High‐performance liquid chromatography coupled with mass spectrometry for the quantitative analysis of vinca‐alkaloids in biological matrices: a concise survey from the literature

“…Strata-X is a polymeric material with reversed-phase properties. Skolnik et al (2006) and Lee et al (2007) also utilized a polymeric reversed-phase material in the form of Oasis HLB columns for the simultaneous bioanalysis of vincristine and actinomycin-D. Oasis HLB columns are also described in a study about the metabolism of vinorelbine (De Graeve et al, 2008).…”