Doxorubicin phosphate

Stock solutions of anthracyclines (1 mg/mL) were prepared in double distilled water and stored at 4°C in the dark. Standard working solutions were prepared by diluting stock solutions with double distilled water or 0.1 M phosphoric acid. Aliquots of blank human plasma (0.5 mL) were spiked with working solutions of anthracyclines, mixed with 0.5 mL of 0.2M dibasic sodium phosphate buffer (pH 8.4), extracted with 4 mL of chloroform 1-heptane (9 1 v/v) by shaking for 15 min and centrifuged at 4000 rpm for 10 min. The lower organic layer was re-extracted with 0.25 mL of 0.1M phosphoric acid. The upper aqueous layer was collected and assayed. The injection volume was 50 fiL. Retention times for daunorubicinol, daunorubicin, idarubicinol, idarubicin, doxorubicinol, doxorubicin, epirubicinol, and epirubicin were 6,7, 9.1, 8.0, 11.3, 5.1,6.4, 5.5, and 7.0 min, respectively. 

The initial mixture and each time point are then assayed for doxorubicin and lipid. Lipid concentrations can be quantified by the phosphate assay (see above) or by liquid scintillation counting of an appropriate radiolabel. Doxorubicin is quantified by an absorbance assay (see below). The percent uptake at any time point (e.g., t = 30 minutes) is determined by %-uptake = [(D/L), =30minutes] x 100/[(D/L) inuiai]. Doxorubicin can be assayed by both a fluorescence assay and an absorbance assay, but we find the latter to be more accurate. The standard curve consists of four to five cuvettes containing 0 to 150 nmol doxorubicin in a volume of 0.1 mL samples to be assayed are of the same volume. To each tube is added 0.9 mL of 1% (v/v) Triton X-100 (in water) solution. For saturated lipid systems such as DSPC/Chol, the tubes should be heated in a boiling water bath for 10 to 15 seconds, until the detergent turns cloudy. Samples are allowed to cool, and absorbance is read at 480 nm on a UV/Visible spectrophotometer. 

The initial mixture and each time point are then assayed for ciprofloxacin and lipid. Lipid can be quantified using the phosphate assay (64,65) or by liquid scintillation counting. Ciprofloxacin is quantified by an absorbance assay following removal of drug from lipid by a Bligh-Dyer extraction procedure (78) (see below). The percent uptake is determined as described in the section Remote Loading of Doxorubicin into DSPC/Cholesterol (55 45) Large Unilamellar Vesicle. ... 

Physically compatible up to 48 hours - Ascorbic acid benztropine cytarabine dexamethasone sodium phosphate diphenhydramine doxorubicin heparin sodium hydrocortisone sodium phosphate lidocaine magnesium sulfate multivitamin infusion (must be refrigerated) vitamin B complex with ascorbic acid. 

The dimers were studied more closely in HL-60 leukaemia and Jurkat cell lines, and it was found that they have activities comparable to the clinically nsed anticancer drng doxorubicin. In terms of general toxicity to normal cells, it was observed that dimers 115 and 116 were not toxic to lymphocytes at doses approaching 100 p,M. In preliminary studies, apoptotic cell death was observed on exposnre to these componnds and further studies are ongoing to elucidate the underlying mechanism of apoptosis. For purposes of comparison, the corresponding phosphate ester monomers 117 and 118 were prepared and proved to have no antitumour activity in the cell lines examined. This result is important, because it rules out any role of the phosphate ester functionality in mediating the observed cytotoxic effects and emphasizes the necessity for a bivalent unit. 

Kwon et al. (1997) applied reversed-phase HPLC to determine doxorubicin (DOX) loading in PEO-bPBLA micelles. Samples of 20 mL diluted to jk /mL DOX with 0.10 M sodium phosphate buffer, pH 7.4, were separated af4Dat a low rate of 1.0 mL/min. The mobile phase was a linear gradient mixture of an aqueous solution of 1 % acetic acid and ACN (15% v/vto 85% v/v). Detection of DOX was done by measuring its UV absorbance at 485 nm. 

Gao, J.-P. et al. (1993) The role of reduced nicotinamide adenine dinucleotide phosphate in glucose- and temperature-dependent doxorubicin cytotoxicity, Cancer Chemother. Pharmacol. 33, 191-196. 

Hydrogen sulfide Polychlorinated biphenyls Tri-o-tolyl phosphate Cisplatin Chlorpromazine Doxorubicin Thalidomide Valproic acid Botulinum toxin... 

Fritze A, Hens F, Kimpfler A, Schubert R, Peschka-Siiss R (2006) Remote loading of doxorubicin into liposomes driven by a transmembrane phosphate gradient. Biochim Biophys Acta 1758 1633-1640... 

Myelosuppression mucositis worse with continuous infusion moderately emetogenic may cause acute and delayed (by 24 8 hours) emesis vesicant severe extravasation injury cardiotoxicity (similar to other anthracyclines) may be less cardiotoxic than doxorubicin controversy about equ ivalent doses cardiac toxicity associated with cumulative doses >900 mg/m Myelosuppression moderately emetogenic may be worse with oral and high-dose regimens alopecia mucositis hypotension infusion rate-related etoposide phosphate can be given IV push without hypotension risk hypersensitivity reactions especially common in children... 

Doxorubicin and metabolite, daunorubicin and metabolite Serum LLE/acetonitrile protein precipitation Sodium phosphate, pH 5.0, 60nmoll spermine, 70% acetonitrile Patient samples... 

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