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Carboplatin
Molecular formula: C6H12N2O4Pt Molecular weight: 371.3 CAS Registry No.: 41575-94-4

SAMPLE Matrix: blood Sample preparation: 500 |xL Plasma + 500 JJLL MeCN: MeOH: water 10:40:50, vortex, filter through a Centricon-10 10000 molecular mass cut-off filter (Amicon) with centrifuging at 2677 g for 30 min, inject a 10-30 |xL aliquot of the ultrafiltrate. HPLCVARIABLES Column: 100 X 4.6 3 |mm Spherisorb phenyl Mobile phase: MeOH: water 5:95 for 5 min then MeCN: MeOH: isopropanol: water 45:45 :5:5 at 2.5 mL/min, re-equilibrate with MeOH:water 5:95 for 10 min Column temperature: 50 Flow rate: 0.5 Injection volume: 10-30 Detector: UV 210 CHROMATOGRAM Retention time: 3.6 Limit of detection: 10 ppb (100 |xL injection) KEYWORDS plasma; dog; ultrafiltrate REFERENCE
Tyczkowska, K.; Page, R.L.; Riviere, J.E. Determination of carboplatin in canine plasma by liquid chromatography with ultraviolet-visible detection and confirmation by atomic absorption spectroscopy. J.Chromatogr., 1990, 527, 447-453

SAMPLE Matrix: blood, urine Sample preparation: Plasma. Filter (Amicon MPS-I with a YMT membrane) while centrifuging at 3000 g at 4 for 15 min, inject an aliquot of the ultrafiltrate. Urine. Inject an aliquot directly. HPLCVARIABLES Column: 250 X 4.6 Inertsil ODS-2 Mobile phase: MeCN: 10 mM pH 5.5 buffer 5:95 Column temperature: 40 Flow rate: 1 Injection volume: 100 Detector: UV 290 following post-column derivatization. The column effluent mixed with the reagent pumped at 0.3 mL/min and the mixture flowed through a 10 m X 0.5 mm i.d. coil of PTFE tubing held at 60 to the detector. (The reagent was 40 mM sodium bisulfite and 10 mM acetate buffer, pH 5.5.) CHROMATOGRAM Retention time: 6.5 Limit of detection: 60 nM

OTHER SUBSTANCES Simultaneous: oxaliplatin, tetraplatin KEYWORDS plasma; ultrafiltrate; rabbit; human; post-column reaction REFERENCE
Kizu, R.; Yamamoto, T.; Yokoyama, T.; Tanaka, M.; Miyazaki, M. A sensitive postcolumn derivatization/UV detection system for HPLC determination of antitumor divalent and quadrivalent platinum complexes. Chem.Pharm.BulL, 1995, 43, 108-114

SAMPLE Matrix: formulations Sample preparation: Dilute with mobile phase, inject an aliquot. HPLCVARIABLES Column: 300 X 4.6 5 um C18 Mobile phase: water Flow rate: 2.5 Injection volume: 20 Detector: UV 228 CHROMATOGRAM Retention time: 3.10 KEYWORDS stability-indicating; injections; saline REFERENCE
Mayron, D.; Gennaro, A.R. Stability and compatibility of granisetron hydrochloride in i.v. solutions and oral liquids and during simulated Y-site injection with selected drugs. Am.J.Health-Syst.Pharm., 1996, 53, 294-304

SAMPLE Matrix: formulations Sample preparation: Emulsion. 500 |xL Emulsion + 1 0 mL 400 |xg/mL hydroquinone in MeOH + 40 mL 0.1% Tween 80, shake until homogeneous, inject a 10 |JLL aliquot. Drug release medium. 1 mL Drug release medium + 200 |xL 100 |xg/mL hydroquinone, mix, inject a 50 |xL aliquot. HPLCVARIABLES Column: 250 X 4.6 10 |xm Cosmosil 10 C18 (Nacalai Tesque) Mobile phase: Gradient. MeCN: 10 mM pH 3.0 phosphate buffer 2:98 for 1 min, to 45:55 over 5.5 min, maintain at 45:55 for 2 min, return to initial conditions over 1 min. Flow rate: 2 Injection volume: 10-50 Detector: UV 220 CHROMATOGRAM Retention time: 2.2 Internal standard: hydroquinone (4.2) Limit of detection: 500 ng/mL OTHER SUBSTANCES Simultaneous: epirubicin, mitomycin C, iomeprol

KEYWORDS emulsions; drug release medium; injections REFERENCE Yamazoe, K.; Horiuchi, T.; Sugiyama, T.; Katagiri, Y. Simultaneous high-performance liquid chromatographic determination of carboplatin, epirubicin hydrochloride and mitomycin C in a Lipiodol emulsion. J.Chromatogr.A, 1996, 726, 241-245 SAMPLE Matrix: formulations Sample preparation: Adjust pH to 7.0, dilute if necessary, inject an aliquot. HPLCVARIABLES Column: 150 X 4.2 5 |xm Nucleosil C18 Mobile phase: 10 mM pH 7.0 phosphate buffer containing 0.55 mM hexadecyltrimethylammonium bromide (Condition column before use with 0.5% hexadecyltrimethylammonium bromide.) Flow rate: 1 Detector: UV 216 CHROMATOGRAM Retention time: 3 Limit of detection: 1 |xg/mL Limit of quantitation: 5 |xg/mL OTHER SUBSTANCES Simultaneous: cisplatin KEYWORDS infusion fluids; stability-indicating REFERENCE Rochard, E.; Boutelet, H.; Griesemann, E.; Barthes, D.; Courtois, P. Simultaneous high performance liquid chromatographic analysis of carboplatin and cisplatin in infusion fluids. J.Liq.Chromatogr., 1993, 16, 1505-1516

ANNOTATED BIBLIOGRAPHY Prat, J.; Pujol, M.; Girona, V.; Munoz, M.; Sole, L.A. Stability of carboplatin in 5% glucose solution in glass, polyethylene and polypropylene containers. J.Pharm.Biomed.Anal., 1994,12, 81-84 [stabilityindicating; 5% dextrose] Hadfield, J.A.; McGown, A.T.; Dawson, M.J.; Thatcher, N.; Fox, B.W. The suitability of carboplatin solutions for 14-day continuous infusion by ambulatory pump: an HPLC-dynamic FAB study. J.Pharm.Biomed.AnaL, 1993, 11, 723-727 Allsopp, M.A.; Sewell, G.J.; Rowland, CG. A column-switching liquid chromatography assay for the analysis of carboplatin in plasma ultrafiltrate. J.Pharm.Biomed.Anal., 1992, 10, 375-381 Duncan, G.F; Faulkner, H.C; Farmen, R.H.; Pittman, K.A. Liquid chromatographic procedure for the quantitative analysis of carboplatin in beagle dog plasma ultrafiltrate. J.Pharm.ScL, 1988, 77, 273-276 Elferink, F ; van der Vijgh, W.J.; Pinedo, H.M. On-line differential pulse polarographic detection of carboplatin in biological samples after chromatographic separation. Anal.Chem., 1986, 58, 2293-2296 Gaver, R.C.; Deeb, G. High-performance liquid chromatographic procedures for the analysis of carboplatin in human plasma and urine. Cancer ChemotherPharmacol., 1986, 16, 201206 Ding, X.-D.; Krull, LS. Dual electrode liquid chromatography-electrochemical detection (LCEC) for platinum-derived cancer chemotherapy agents. J.Liq.Chromatogr., 1983, 6, 2173-2194