Capillary Liquid Chromatography with UV Detection Using <i>N</i>,<i>N</i>-Diethyl Dithiocarbamate for Determining Platinum-Based Antitumor Drugs in Plasma

Abstract

A capillary liquid chromatography with UV detection (CLC-UV) system has been developed for determining platinum-based antitumor drugs (e.g., cisplatin, carboplatin, and nedaplatin) in plasma based on the pre-column derivatization of platinum with N,N-diethyl dithiocarbamate (DDTC). The chelated platinum separation was carried out on a capillary column (Inertsil ODS-3, 150 mm 0.3 mm i.d., 3 µm) using an acetonitrile-water mixture (8 : 2, v/v) as a mobile phase that flowed at 5.0 µL/min. Detection was carried out by absorbance at 254 nm. Chromatographic peak height was found to be linearly related to the spiked concentration of nedaplatin in the blank control plasma from 5.0 ng/mL to 15 µg/mL (r 2 >0.998). The repeatability (n 5) of the chromatographic peak height for 2.5 µg/mL nedaplatin was 2.6% relative standard deviation (R.S.D.). The CLC-UV system, which required only 20 µL of plasma sample, was applied to the determination of total and free form platinum-based antitumor drugs in plasma after injection into rats. The recovery rates (n 5) of total and free form nedaplatin in plasma were 98% and 99%, respectively, and these repeatability were 2.4% R.S.D. and 3.1% R.S.D., respectively. In addition, the recovery rates (n 5) of total and free form carboplatin in plasma were 99% and 99%, respectively, and these repeatability were 2.9% R.S.D. and 0.24% R.S.D., respectively. The concentration-time profiles of total and free form nedaplatin in rat plasma were monitored to determine the pharmacokinetic parameters.Key words platinum-based antitumor drug; plasma; capillary column; liquid chromatography Platinum-based antitumor drugs, including cisplatin, carboplatin, oxaliplatin, and nedaplatin are used to treat various types of cancers, such as sarcomas, carcinomas, etc. Nedaplatin, cis-diammineglycolatioplatinum, is a second-generation platinum agent that is approximately 10 times as soluble in water as cisplatin. [1][2][3][4] As such, nedaplatin is considered to have more pronounced activity against solid tumors, but less nephrotoxicity and gastrointestinal toxicity than cisplatin.

Using HPLC for the determination of platinum drugs in biological matrixes after derivatization with diethyldithiocarbamate

“…The protocols published elsewhere reported derivatization at 37–60°C for 10–60 min [27, 33–37, 45, 46]. We performed the cisplatin reactions at 20, 40, and 45°C.…”

“…To determine unbound or total platinum as a DDTC complex, PUF had to be obtained. The current literature presents several methods for its preparation, most of them focusing on the use of membranes with different pore sizes [27,[45][46][47]. Interestingly, no difference in quality was observed when using membranes with a cut-off of 3 and 30 kDa for the molecules to obtain the free platinum drug [48].…”

Recent Upgradation in Bioanalytical Studies

“…Initially, detection was achieved using liquid chromatography with an ultraviolet detector (LC-UV), but mass spectrometry was subsequently used to upgrade the method (MS). 2 Because pharmaceutical medications are non-volatile, thermolabile, and polar, they are not suited for gas chromatography (GC). UV, fluorescence, and electrochemical detection are the most prevalent LC detection methods.…”

An Exploration of Advancement in Analytical Methodology for Quantification of Anticancer Drugs in Biomatrices

“…It works on the principle of adsorption or partitioning between two phases. Chromatography can be of different types, such as gas chromatography, liquid chromatography, supercritical fluid chromatography, capillary liquid chromatography with UV detector, 10 thin layer chromatography, etc. Each has separate applications along with advantages and disadvantages.…”