Identification of degradation products from aqueous carboplatin injection samples by electrospray mass spectrometry

Kannan, Vivekanandan; Swamy, Madugundu Guru; Prasad, Sudhanand; Maikap, Golak C.; Mukherjee, Rama; Burman, Anand C.

doi:10.1016/j.ijpharm.2006.02.002

Cited by 13 publications

(11 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Identification and structural elucidation of paclitaxel impurities in API beyond threshold limits (0.1%) is mandatory based on the International Conference on Harmonisation (ICH) guidelines 11. There have been a number of reports on strategies involved in identification and structural elucidation of impurities that appear in API12–15 and quantification of related impurities in finished paclitaxel pharmaceutical formulations 16, 17. Although the discovery of electrospray techniques contributed a great deal to the development of new drug candidates, identification of molecular ions of trace level impurities could not be conclusive, due to alkali metal ion adduct formation.…”

Section: Components Of Taxus Brevifolia Extract10mentioning

confidence: 99%

Identification of isocephalomannine in the presence of cephalomannine isomers and alkali metal ion adducts in a paclitaxel active pharmaceutical ingredient using electrospray tandem mass spectrometry

Kannan¹,

Swamy²,

Prasad³

et al. 2006

Rapid Comm Mass Spectrometry

View full text Add to dashboard Cite

A strategy is developed for the identification of isocephalomannine in the presence of alkali metal ion adducts and other cephalomannine isomers in a paclitaxel active pharmaceutical ingredient. Intact molecular ion analyses and a sub-structural study have been performed for the differentiation of isocephalomannine (2-debenzoylpaclitaxel-2-pentenoate) from cephalomannine and 7-epi-cephalomannine. A comparative study of the cephalomannine isomers was carried out using molecular ions (MS) and fragmentation patterns (MS/MS) for sub-structural analysis. An attempt has been made to identify isocephalomannine in Cremophor(R) EL formulations.

show abstract

Section: Components Of Taxus Brevifolia Extract10mentioning

confidence: 99%

Identification of isocephalomannine in the presence of cephalomannine isomers and alkali metal ion adducts in a paclitaxel active pharmaceutical ingredient using electrospray tandem mass spectrometry

Kannan¹,

Swamy²,

Prasad³

et al. 2006

Rapid Comm Mass Spectrometry

View full text Add to dashboard Cite

show abstract

“…ESI-MS was employed as detector for carboplatin and IS (carboplatin-d4), which made measurement of intact carboplatin precisely. Unlike the method of AAS or ICP-MS measuring platinum as an element, ESI-MS technique that ionizes F I G U R E 2 Percent intact carboplatin following storage of plasma samples with different anticoagulants at room temperature for 0-4 h chemical species and sorts the ions based on their mass-tocharge ratio can detect intact carboplatin directly [6,24]. As we all know, four major nature isotopes of platinum are 194 Pt,195 Pt,196 Pt and 198 Pt, and their natural abundances of 32.9, 33.9, 25.3 and 7.2% [6,10,15].…”

Section: Esi-ms Methods Developmentmentioning

confidence: 99%

A novel and fully validated hydrophilic interaction liquid chromatography with tandem mass spectrometry method for the determination of intact carboplatin in human plasma

Ren

Qin

Fan

et al. 2018

Separation Science Plus

View full text Add to dashboard Cite

Carboplatin is an anticancer drug widely used to treat a variety of cancers. However, a simple, sensitive and rapid method for the quantitation of intact carboplatin is still absence for therapeutic drug monitoring or clinical trials. In this work, a rapid, universal, and reliable hydrophilic interaction liquid chromatography with tandem mass spectrometry method for the determination of intact carboplatin in human plasma was developed and fully validated. Carboplatin was extracted from human plasma by simple protein precipitation with acetonitrile. A good chromatographic separation of carboplatin was achieved on a Waters XBridge HILIC column (2.1 × 150 mm, 3.5 μm), with the analytical time 5.5 min for one sample. The linearity range of the assay was from 10 to 2000 ng/mL. The method was linear (r2 > 0.9989), accurate (<6% bias, 12% bias at LOQ) and precise (intra‐day and inter‐day precision of <3% coefficient of variation). The stability of intact carboplatin in human plasma with three different anticoagulants was assessed in this study. Furthermore, the matrix effect of hemolysis and hyperlipidemic samples was also evaluated for the first time. This work made the routine determination of intact carboplatin feasible and universal in clinical practice.

show abstract

“…In another report, Guo and coworkers studied relatively high concentrations of carboplatin (3 mM) using mass spectrometry and reported the existence of a dimer, trimer, and tetramer of the drug [20]. The dimer of carboplatin was also observed in mass spectroscopic studies by Vivekanandan et al [21] and later by us [18,22]. Although mass spectrometry is an ideal way to detect association complexes, solution samples that are injected into the spectrometer are condensed.…”

Section: Self-association Of Carboplatin In Its Ready-to-use Infusionmentioning

confidence: 96%

Understanding how the platinum anticancer drug carboplatin works: From the bottle to the cell

Pasqua

Goodisman

Dabrowiak

2012

Inorganica Chimica Acta

View full text Add to dashboard Cite

Carboplatin, a platinum anticancer drug used to treat many types of human cancer, contains a bidentate dicarboxylate chelate leaving ligand, a structural feature that makes it much less chemically reactive than the first-generation platinum anticancer drug cisplatin, which contains two monodentate chloride leaving ligands. In water, carboplatin exists in a monomer-dimer equilibrium with an association constant of K (M À1) % 391, a property that accounts for the long-term stability of its readyto-use infusion solution. When administered in the clinic, carboplatin is believed to exert its biological effects by interacting with genomic DNA and proteins. The slower substitution kinetics of carboplatin, compared to cisplatin, has prompted investigators to focus on mechanisms by which the compound can be activated in vivo. Carbonate, which is in equilibrium with hydrogen carbonate, carbonic acid, and dissolved carbon dioxide, is ubiquitous in biological systems, and is found in high concentrations in the blood, the interstitial fluid, and the cytosol. Activation of carboplatin by carbonate, CO 3 2À (k 1 = 2.04 ± 0.81 Â 10-6 in 24 mM carbonate buffer, pH 7.5 at 37°C), for example, leads to the formation of platinum species that are more cytotoxic than the parent drug. This short review focuses on the reason for the unusual stability of carboplatin in its aqueous ready-to-use infusion solution, describes the reactions of the drug with biologically common nucleophiles and summarizes the activation chemistry that make the drug more reactive toward substances present in the biological system.

show abstract

Identification of degradation products from aqueous carboplatin injection samples by electrospray mass spectrometry

Cited by 13 publications

References 12 publications

Identification of isocephalomannine in the presence of cephalomannine isomers and alkali metal ion adducts in a paclitaxel active pharmaceutical ingredient using electrospray tandem mass spectrometry

Identification of isocephalomannine in the presence of cephalomannine isomers and alkali metal ion adducts in a paclitaxel active pharmaceutical ingredient using electrospray tandem mass spectrometry

A novel and fully validated hydrophilic interaction liquid chromatography with tandem mass spectrometry method for the determination of intact carboplatin in human plasma

Understanding how the platinum anticancer drug carboplatin works: From the bottle to the cell

Contact Info

Product

Resources

About