A novel method for speciation of Pt in human serum incubated with cisplatin, oxaliplatin and carboplatin by conjoint liquid chromatography on monolithic disks with UV and ICP-MS detection

New method for the speciation of ruthenium-based chemotherapeutics in human serum by conjoint liquid chromatography on affinity and anion-exchange monolithic disks

“…The same chromatographic procedure as was previously applied for separation of Pt-based chemotherapeutics [37] was used further for separation of Ru species. Briefly, in the first minute isocratic elution with 100% buffer A was applied to elute unbound (UB) Ru-based chemotherapeutic, followed by linear gradient elution from buffer A to 50% buffer B in the next 9 min, in order to separate Tf from HSA.…”

“…Due to such characteristics, monoliths are frequently used in chromatographic separations of biomolecules, organic acids and purification of viruses [28][29][30][31] while their use in speciation analysis is scarce. Examples of successful application of monolithic chromatography in speciation analysis are the investigations on Al speciation in human serum [32,33], Zn in human milk [34], Ni in tea infusions [35], the study of the distribution of cisplatin [36] in serum of cancer patients and the investigation of the kinetics of the interaction and distribution of Ptbased chemotherapeutics with proteins in blood serum [37]. In the study of the distribution of cisplatin in human serum [36], Pt fractionation was performed first by SEC on a HiTrap desalting column to separate unbound Pt from Pt bound to serum proteins.…”

“…In the study of the distribution of cisplatin in human serum [36], Pt fractionation was performed first by SEC on a HiTrap desalting column to separate unbound Pt from Pt bound to serum proteins. Protein peak was collected and speciation of Pt performed by CIM DEAE-1 monolithic column coupled to ICP-MS. Conjoint liquid chromatography (CLC) on short monolithic disks, which was used for fast analysis of impurities in immunoglobulin concentrates [38], was applied also for speciation of metallodrugs [37]. In this innovative approach simultaneous two-dimensional separation of ionic forms of Pt-based chemotherapeutics from the portions bound to different serum proteins was possible in one chromatographic run by assembling affinity CIM Protein G disk and anion-exchange CIM DEAE disk in a single housing, forming a CLC monolithic column.…”

“…On the first disk chemotherapeutic bound to immunoglobulin G was separated, while on the second disk unbound form of chemotherapeutic was separated from the portion bound to human serum albumin (HSA) and transferrin (Tf). In combination with UV and ICP-MS detection, in which accurate quantification of separated Pt species was performed by post-column ID-ICP-MS technique, the kinetics of binding of cisplatin, carboplatin and oxaliplatin to serum proteins was studied in spiked human serum [37].…”

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

“…272,273 Better LOQ's, between 2 and 25 ng mL −1 , were reached with LC-MS. [274][275][276][277][278] However, the technique of choice for the detection of platinum derivatives was undoubtedly inductively coupled plasma mass spectrometry (ICP-MS). ICP-MS coupled to a separation technique, [279][280][281][282][283][284]285 or not, 21,286,287 is characterised by an excellent LOQ, in the range 0.1 to 1 µg mL −1 . A chromatogram obtained for the analysis of platinum compounds by LC-ICP-MS is reported in Fig.…”