Distribution study of cisplatin in rat kidney and liver cancer tissues by using liquid chromatography electrospray ionization tandem mass spectrometry

Abstract

A sensitive and rapid liquid chromatography positive ion electrospray ionization tandem mass spectrometric (LC/ESI-MS/MS) method has been developed and validated for the quantitative determination and distribution of cisplatin (CP) in kidney and liver tissues after intravenous administration of drug to adult male Sprague Dawley rats. Oxaliplatin (OXP) was used as an internal standard. The tissue samples were homogenized and extracted using conventional liquid-liquid extraction method with phosphate buffer containing ethyl acetate and then subjected to LC-MS analysis. The chromatographic separation was achieved on an Agilent ZORBAX SB C-18 column (50 × 2.1 mm, 1.8 µm) using the mobile phase consisting of 0.1% formic acid in water (Solvent A) : methanol (Solvent B) (40 : 60; v/v) in an isocratic elution followed by detection with positive ion electrospray ionization tandem mass spectrometry using the transitions of m/z 301 > 265 for CP and m/z 398 > 310 for OXP in multiple reaction monitoring mode. The calibration curve was linear in the range of 5.0-7000 and 10.0-6000 ng/ml for kidney and liver tissue homogenates, respectively. The method revealed good performances in terms of within-batch, between-batch precision (1.31-5.70%) and accuracy (97.0-102.24%) for CP in both kidney and liver tissue homogenates including lower and upper limits of quantification. The recoveries from spiked control samples were >81.0% and >87.0 % for CP and OXP, respectively. Matrix effect was found to be negligible, and the stability data were within the acceptable limits. Further, the validated LC/ES-MS/MS method was successfully applied to investigate the distribution of CP in kidney and liver tissues after intravenous administration of CP to male Sprague Dawley rats. The results showed that the higher amount of CP was distributed in kidney followed by liver, which indicated that CP mainly accumulated in kidney tissues and renal excretion might be a primary and main elimination route. This is the first research approach focused on the quantitative determination and distribution of CP in rat kidney and liver tissue homogenates by using LC/ESI-MS/MS, which could provide essential information for further pharmacological and clinical studies of CP.

Zwitterionic hydrophilic interaction liquid chromatography-tandem mass spectrometry with HybridSPE-precipitation for the determination of intact cisplatin in human plasma

“…As shown in Fig.1 labeled as "Column 6" and "Column 7", a retention factor of less than 0.30 was obtained for these two columns, which is consistent with previous findings ("column 3" and "Column 4" in Fig.1) [8,31]. However, there is quite a divergence in the retention factor for cisplatin when compared to a more recent publication (labeled as "Column 5" in Fig.1) where they found a retention factor of 5.91 on a Zorbax SB C18 column by using 0.1% formic acid in water/methanol (40:60, v/v) as the MP [35].…”

“…Selective methods for the determination of cisplatin itself in biological matrices are based on HPLC followed by different kinds of on-line or off-line detectors such as radioactivity detection [27], UV detection [10,16,[28][29][30], flameless atomic absorption spectrometry (FAAS) [15], ICP-MS [31][32][33][34] and MS/MS [35]. UV-based methods usually require pre-column or post-column derivatization due to the low molar absorptivity of cisplatin in the UV spectrum [10,[28][29][30]36].…”

“…Although this approach can promote the ionization of cisplatin, it results in a measurement of cisplatin together with other Pt-based complexes aforementioned. To our knowledge, only one LC-MS/MS method has been described for the quantification of intact cisplatin in rat kidney and liver [35].…”

“…However, this does not alleviate the instability of cisplatin in the aqueous environment of the ultrafiltrate: cisplatin is also highly susceptible to hydrolysis. The above mentioned LC-MS/MS assay uses a conventional liquid-liquid extraction followed by a tedious evaporation procedure [35]. As such, it does not meet the requirements for a high throughput determination of cisplatin in biological fluids such as plasma.…”

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

“…[269][270][271] The introduction of an additional derivatisation step improved sensitivity (up to a factor of 100) with LC-UV methods. 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 .…”