Liquid chromatography‐mass spectrometry for the quantitative bioanalysis of anticancer drugs

Abstract

The monitoring of anticancer drugs in biological fluids and tissues is important during both pre‐clinical and clinical development and often in routine clinical use. Traditionally, liquid chromatography (LC) in combination with ultraviolet (UV), fluorescence, or electrochemical detection is employed for this purpose. The successful hyphenation of LC and mass spectrometry (MS), however, has dramatically changed this. MS detection provides better sensitivity and selectivity than UV detection and, in addition, is applicable to a significantly larger group of compounds than fluorescence or electrochemical detection. Therefore, LC‐MS has now become the method of first choice for the quantitative bioanalysis of many anticancer agents. There are still, however, a lot of new developments to be expected in this area, such as the introduction of more sensitive and robust mass spectrometers, high‐throughput analyses, and further optimization of the coupled LC systems. Many articles have appeared in this field in recent years and are reviewed here. We conclude that LC‐MS is an extremely powerful tool for the quantitative analysis of anticancer drugs in biological samples. © 2004 Wiley Periodicals, Inc., Mass Spec Rev 24:887–917, 2005

A Phase I, Randomized, Open-Label, Parallel-Cohort, Dose-Finding Study of Elacridar (GF120918) and Oral Topotecan in Cancer Patients

“…In brief, 1 mL of cold methanol of -30jC was added to 1 mL of plasma to retain the ratio between lactone and carboxylate of topotecan. Plasma samples were assayed for topotecan lactone, for total topotecan, and for elacridar (only in part I) using validated liquid chromatography-tandem mass spectrometry methods (23,24).…”

The use of liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring of antibiotics in cancer patients

“…To date all the studies comments on the anticancer related toxicities associated with the concomitant presence of antibiotics but none evaluated the presence of anticancer drugs on the PK/PD of antibiotics which remains an interesting field of research that merits further investigation. Finally, TDM is not only important to adjust the dose of antimicrobial therapy and the anticancer therapy [15] but such monitoring will also help in identifying and avoiding drug potential interactions.…”

“…Collectively, as the pathophysiological changes observed in critically ill patients differ widely inter-and intraindividually and due to the potential occurrence of drugdrug interaction, the establishment of specific guidelines to be used by the clinicians is unlikely to be successful [12][13][14]. Consequently, by tailoring the antimicrobial therapy and monitoring antibiotic-antineoplastic interaction, therapeutic drug monitoring (TDM) would serve as an invaluable tool to increase the efficacy and safe therapeutic use of both classes of drugs in critically ill/immunocompromised patients [15]. To be applied in routine analysis the method(s) used for TDM has to be fast, accurate and cost effective.…”

A Stability-Indicating High Performance Liquid Chromatographic Method For the Determination of Nelarabine

“…For stability studies 2mL of sample was taken from the nelarabine injection solution (250mg/50mL) into a 100mL volumetric flask and diluted up to the mark using mobile phase 7,8 . Acid hydrolysis of the drug was carried out in presence of 1.5N HCl.…”