Abstract
Cisplatin and its analogues are widely used as chemotherapeutic agents in clinical practice. After being intravenously administrated, a substantial amount of platinum will bind with proteins in the blood. This binding is vital for the transport, distribution, and metabolism of drugs; however, toxicity can also occur from the irreversible binding between biologically active proteins and platinum drugs. Therefore, it is very important to study the protein-binding behavior of platinum drugs in blood. This review summarizes mass spectrometry-based strategies to identify and quantitate the proteins binding with platinum anticancer drugs in blood, such as offline high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC–ICP-MS) combined with electrospray ionization mass spectrometry (ESI-MS/MS) and multidimensional LC–ESI-MS/MS. The identification of in vivo targets in blood cannot be accomplished without first studying the protein-binding behavior of platinum drugs in vitro; therefore, relevant studies are also summarized. This knowledge will further our understanding of the pharmacokinetics and toxicity of platinum anticancer drugs, and it will be beneficial for the rational design of metal-based anticancer drugs.
Highlights
The identification of in vivo targets in blood cannot be accomplished without first studying the protein-binding behavior of platinum drugs in vitro; relevant studies are summarized
24 h after infusion, the protein-b rate (PBR) for cisplatin is 98%, and the binding of platinum to protein is basical curve (AUC), and the AUC of carboplatin is closely correlated with its clinical parameters, including toxicity and response [16,19,25,26]
The same platinum-modified peptides were found in the MS spectra of both the cisplatin–protein mixture and the human blood serum digests from the same isoelectric focusing (IEF) fractions, and they were assigned as platinated peptides of human serum albumin (HSA)
Summary
Cisplatin (Figure 1), which was discovered by Rosenberg in the 1960s, is the first metal complex to exhibit antitumor activity [1]. Oxaliplatin lation and protein-binding behavior of platinum drugs in plasma have a great im t1/2α (min) their pharmacokinetics, for example renal excretion rate [6,17,18]. 24 h after infusion, the protein-b rate (PBR) for cisplatin is 98%, and the binding of platinum to protein is basical curve (AUC), and the AUC of carboplatin is closely correlated with its clinical parameters, including toxicity and response [16,19,25,26]. Carboplatin is mainly excreted through the kidneys [27] Oxaliplatin, another commonly used antitumor drug, binds to protein at a high ratio; it can bind to erythrocytes [11]. They are less frequently used in the relevant studies
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