Development of HPLC conditions for valid determination of hydrolysis products of cisplatin

El-KhateebM, AppletonTG, Charles, BG and GahanLR (1999) Development of HPLC conditions for valid determination of hydrolysis products of cisplatin. Journal of Pharmaceutical Sciences, 88 3: 319-326. doi:10.1021/js980287m

Author El-KhateebM
Charles, BG
Title Development of HPLC conditions for valid determination of hydrolysis products of cisplatin
Journal name Journal of Pharmaceutical Sciences   Check publisher's open access policy
ISSN 0022-3549
Publication date 1999
Sub-type Article (original research)
DOI 10.1021/js980287m
Volume 88
Issue 3
Start page 319
End page 326
Total pages 8
Place of publication Columbus, USA
Publisher American Chemical Society
Collection year 1999
Language eng
Subject C1
780103 Chemical sciences
250204 Bioinorganic Chemistry
Abstract In water, the antineoplastic drug cisplatin, cis-[PtCl2(NH3)(2)] (1) hydrolyses slowly to the aqua complexes cis-[Pt(NH3)(2)Cl(H2O)](+) (2) and, to a small extent, cis-[Pt(NH3)(2)(H2O)(2)](2+) (3), which are thought to play an important role in the metabolism of cisplatin. HPLC is a useful technique for monitoring 2 and 3, but only if the components of the mobile phase used in the reverse phase HPLC technique are unreactive toward these aqua complexes under the conditions of the experiment. N-15 Nuclear magnetic resonance (NMR) with samples highly enriched (>98%) in N-15 has been used to check the reactivity of 2 and 3 toward substances commonly used as components of the mobile phase. The results reported herein indicate that acetonitrile, often used as an organic modifier, reacts readily with 2 and 3. Methanol, also commonly employed, is much less reactive. Carboxylic acids RCO2H (R = CH3, H, CF3), which are frequently used to adjust pH of the mobile phase, also react readily with 2 and 3. Trifluoromethanesulfonic acid (triflic acid), CF3SO3H, is unreactive. Neither hexanesulfonic acid nor sodium dodecyl sulfate (SDS), used as ion-pairing agents, reacts significantly with 2 or 3 under the experimental conditions, but SDS gives better peak separation. Commercial SDS must, however, be purified from chloride contamination. From our studies, optimal conditions for HPLC separation of 1, 2, and 3, with a Gls stationary phase at 37 degrees C, require an aqueous mobile phase with 3% v/v methanol, 0.05 mM SDS, and pH 2.5 (adjusted with triflic acid). This technique was then used to measure revels of 1, 2, and 3 in ultrafiltered serum after incubation for Various times with cisplatin at 37 degrees C.
Keyword Chemistry, Medicinal
Chemistry, Multidisciplinary
Pharmacology & Pharmacy
Bridged Platinum(ii) Complexes
Spectrometric Detection
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemical Engineering Publications
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Citation counts: TR Web of Science Citation Count  Cited 35 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 10 Jun 2008, 13:42:26 EST