Capecitabine (formerly RO 09-1978; RO-09-1978; RO09-1978; CAPE; Trade name: Xeloda) is an anticancer chemotherapeutic medication approved for treating breast cancer, gastric cancer and colorectal cancer. It is a prodrug of fluoropyrimidine carbamate that needs to be converted in vivo into 5-fluorouracil (5-FU), the active form or metabolite.

Physicochemical Properties

Molecular Formula	C15H22FN3O6
Molecular Weight	359.35
Exact Mass	359.149
Elemental Analysis	C, 50.14; H, 6.17; F, 5.29; N, 11.69; O, 26.71
CAS #	154361-50-9
Related CAS #	154361-50-9
PubChem CID	60953
Appearance	White to off-white solid powder
Density	1.5±0.1 g/cm3
Boiling Point	517.6±60.0 °C at 760 mmHg
Melting Point	110-121°C
Flash Point	266.8±32.9 °C
Vapour Pressure	0.0±3.1 mmHg at 25°C
Index of Refraction	1.600
LogP	0.97
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	7
Heavy Atom Count	25
Complexity	582
Defined Atom Stereocenter Count	4
SMILES	FC1C(N([H])C(=O)OC([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=NC(N(C=1[H])[C@@]1([H])[C@@]([H])([C@@]([H])([C@@]([H])(C([H])([H])[H])O1)O[H])O[H])=O
InChi Key	GAGWJHPBXLXJQN-UORFTKCHSA-N
InChi Code	InChI=1S/C15H22FN3O6/c1-3-4-5-6-24-15(23)18-12-9(16)7-19(14(22)17-12)13-11(21)10(20)8(2)25-13/h7-8,10-11,13,20-21H,3-6H2,1-2H3,(H,17,18,22,23)/t8-,10-,11-,13-/m1/s1
Chemical Name	pentyl N-[1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]carbamate
Synonyms	Capecitabine; RO09-1978; Ro-091978000; Ro 091978000; Ro091978000; RO-09-1978; RO 09-1978; Abbreviation: CAPE. Trade name: Xeloda
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	DNA/RNA Synthesis
ln Vitro	Cultivated in the same plates as HepG2 hepatoma, LS174T WT and LS174T-c2 cells exhibit a markedly increased sensitivity to capecitabine, with IC50 values of 890 and 630 μM for LS174T WT alone and HepG2 cultivated similarly. Additionally, when cultivated in the same plates as hepatoma cells, the IC50 for the LS174T-C2 subline decreases from 330 ± 4 to 89 ± 6 μm. Moreover, in thymidine phosphorylase (TP)-transfected LS174T-c2 cells, capecitabine significantly increases apoptotic potential and induces apoptosis in a Fas-dependent manner. There is also a seven-fold increase in cytotoxicity.[1]
ln Vivo	Capecitabine, which can be correlated with tumor dThdPase levels, is more effective in a wider dose range and has a broader spectrum of antitumor activity than 5-FU, UFT, or its intermediate metabolite 5'-DFUR in the human cancer xenograft models studied.[2] Due to the high expression of platelet-derived endothelial cell growth factor in tumors, capecitabine inhibits tumor growth and metastatic recurrence following resection of human hepatocellular carcinoma (HCC) in highly metastatic nude mice model.[3]
Cell Assay	In 96-well plates, HepG2 and LS174T WT or LS174T-c2 cells are seeded in the upper and lower chambers of 8-well strip membranes, respectively. The cells that are expanding exponentially are subjected to escalating levels of capecitabine. When BR17 MoAB is utilized in the experiments, 100 ng/mL of the moab is added to the medium in addition to 750 ng/mL of ZB4 MoAB. The traditional colorimetric MTT test is used to evaluate the viability of LS174T following a continuous exposure of 72 hours.
Animal Protocol	Mice: C57/Bl6 Nu/Nu mice aged six weeks are employed. The procedure involves subcutaneous injection of 107 cells/flank to produce bilateral HCT 116 xenografts. Treatment for animals carrying HCT 116 xenografts involves oral gavage once daily for five days in a row (days 0-4, 7-11, 14-18) with either vehicle or capecitabine 0.52 or 2.1 mmol/kg (563 and 2250 mg/m2, respectively). On days 0 at 15, 30 minutes, 1, 2, 4, 8, and 24 hours, as well as on days 7 and 14 before the scheduled course of treatment, animals are culled. Every time point, three animals are examined. Blood is drawn while in heparin, and the plasma is separated and kept at -80°C. The liver is taken out right away and placed in RNAlater solution for storage. The liver is taken out right away and placed in RNAlater solution for storage. After fibrotic tissue and blood vessels are removed, tumors are macroscopically dissected and liquid nitrogen-frozen.
ADME/Pharmacokinetics	Absorption, Distribution and Excretion The AUC of capecitabine and its metabolite 5’-DFCR increases proportionally over a dosage range of 500 mg/m2/day to 3,500 mg/m2/day (0.2 to 1.4 times the approved recommended dosage). The AUC of capecitabine’s metabolites 5’-DFUR and fluorouracil increased greater than proportional to the dose. The interpatient variability in the Cmax and AUC of fluorouracil was greater than 85%. Following oral administration of capecitabine 1,255 mg/m2 orally twice daily (the recommended dosage when used as a single agent), the median Tmax of capecitabine and its metabolite fluorouracil was approximately 1.5 hours and 2 hours, respectively. Following administration of radiolabeled capecitabine, 96% of the administered capecitabine dose was recovered in urine (3% unchanged and 57% as metabolite FBAL) and 2.6% in feces. In colorectal cancer patients with a mean age of 58 ± 9.5 years and ECOG Performance Status of 0–1, the volume of distribution is calculated to be 186 ± 28 L. In colorectal cancer patients with a mean age of 58 ± 9.5 years and ECOG Performance Status of 0–1, the clearance of capecitabine is calculated to be 775 ± 213 mL/min. Capecitabine is readily absorbed from the GI tract; on average, at least 70% of an oral dose of the drug is absorbed. Although in vitro studies have shown that capecitabine is unstable under highly acidic conditions, the drug appears to be absorbed intact immediately upon dissolution without degradation secondary to the acidic pH of the stomach. According to the manufacturer, peak plasma concentrations of capecitabine occur in about 1.5 hours, and peak plasma concentrations of fluorouracil, its active drug, occur slightly later at 2 hours. In adults with cancer who received a capecitabine dosage of 2510 mg/sq m daily in 2 divided doses, administered approximately 12 hours apart within 30 minutes following the end of a meal, blood samples drawn on day 1 of the treatment cycle showed that peak plasma concentrations of 3.93 and 0.66 ug/mL for capecitabine and fluorouracil, respectively, were achieved in about 2 hours. Considerable interindividual variations (ie, exceeding 85%) in peak plasma concentrations and areas under the concentration-time curves (AUCs) have been reported following oral administration of capecitabine. For more Absorption, Distribution and Excretion (Complete) data for CAPECITABINE (12 total), please visit the HSDB record page. Metabolism / Metabolites Capecitabine undergoes metabolism by carboxylesterase and is hydrolyzed to 5’-DFCR. 5’-DFCR is subsequently converted to 5’-DFUR by cytidine deaminase. 5’-DFUR is then hydrolyzed by thymidine phosphorylase (dThdPase) enzymes to the active metabolite fluorouracil. Fluorouracil is subsequently metabolized by dihydropyrimidine dehydrogenase to 5-fluoro-5, 6-dihydro-fluorouracil (FUH2). The pyrimidine ring of FUH2 is cleaved by dihydropyrimidinase to yield 5-fluoro-ureido-propionic acid (FUPA). Finally, FUPA is cleaved by β-ureido-propionase to α-fluoro-β-alanine (FBAL). Capecitabine, an anticancer prodrug, is thought to be biotransformed into active 5-fluorouracil (5-FU) by three enzymes. After oral administration, capecitabine is first metabolized to 5'-deoxy-5-fluorocytidine (5'-DFCR) by carboxylesterase (CES), then 5'-DFCR is converted to 5'-deoxy-5-fluorouridine (5'-DFUR) by cytidine deaminase. 5'-DFUR is activated to 5-FU by thymidine phosphorylase. Although high activities of drug metabolizing enzymes are expressed in human liver, the involvement of the liver in capecitabine metabolism is not fully understood. In this study, the metabolism of capecitabine in human liver was investigated in vitro. 5'-DFCR, 5'-DFUR, and 5-FU formation from capecitabine were investigated in human liver S9, microsomes, and cytosol in the presence of the inhibitor of dihydropyrimidine dehydrogenase, 5-chloro-2,4-dihydroxypyridine. 5'-DFCR, 5'-DFUR, and 5-FU were formed from capecitabine in cytosol and in the combination of microsomes and cytosol. Only 5'-DFCR formation was detected in microsomes. The apparent K(m) and V(max) values of 5-FU formation catalyzed by cytosol alone and in combination with microsomes were 8.1 mM and 106.5 pmol/min/mg protein, and 4.0 mM and 64.0 pmol/min/mg protein, respectively. The interindividual variability in 5'-DFCR formation in microsomes and cytosol among 14 human liver samples was 8.3- and 12.3-fold, respectively. Capecitabine seems to be metabolized to 5-FU in human liver. 5'-DFCR formation was exhibited in cytosol with large interindividual variability, although CES is located in microsomes in human liver. In the present study, it has been clarified that the cytosolic enzyme would be important in 5'-DFCR formation, as is CES. Capecitabine (Xeloda; CAP) is a recently developed oral antineoplastic prodrug of 5-fluorouracil (5-FU) with enhanced tumor selectivity. Previous studies have shown that CAP activation follows a pathway with three enzymatic steps and two intermediary metabolites, 5'-deoxy-5-fluorocytidine (5'-DFCR) and 5'-deoxy-5-fluorouridine (5'-DFUR), to form 5-FU preferentially in tumor tissues. In the present work, all fluorinated compounds present in liver, bile, and perfusate medium of isolated perfused rat liver (IPRL) and in liver, plasma, kidneys, bile, and urine of healthy rats /were investigated/. Moreover, data obtained from rat urine were compared with those from mice and human urine. According to a low cytidine deaminase activity in rats, 5'-DFCR was by far the main product in perfusate medium from IPRL and plasma and urine from rats. Liver and circulating 5'-DFCR in perfusate and plasma equilibrated at the same concentration value in the range 25 to 400 microM, which supports the involvement of es-type nucleoside transporter in the liver. 5'-DFUR and alpha-fluoro-beta-ureidopropionic acid (FUPA) + alpha-fluoro-beta-alanine (FBAL) were the main products in urine of mice, making up 23 to 30% of the administered dose versus 3 to 4% in rat. In human urine, FUPA + FBAL represented 50% of the administered dose, 5'-DFCR 10%, and 5'-DFUR 7%. Since fluorine-19 nuclear magnetic resonance spectroscopy gives an overview of all the fluorinated compounds present in a sample, we observed the following unreported metabolites of CAP: 1) 5-fluorocytosine and its hydroxylated metabolite, 5-fluoro-6-hydroxycytosine, 2) fluoride ion, 3) 2-fluoro-3-hydroxypropionic acid and fluoroacetate, and 4) a glucuroconjugate of 5'-DFCR. Fluorouracil is catabolized to dihydrofluorouracil (FUH2), a much less toxic metabolite, by dihydropyrimidine dehydrogenase. Dihydropyrimidinase cleaves the pyrimidine ring of dihydrofluorouracil, yielding 5-fluoro-ureido-propionic acid (FUPA), which is then cleaved by beta-ureido-propionase to form alpha-fluoro-beta-alanine (FBAL). Metabolized by thymidine phosphorylase to fluoruracil. Route of Elimination: Capecitabine and its metabolites are predominantly excreted in urine; 95.5% of administered capecitabine dose is recovered in urine. Fecal excretion is minimal (2.6%). The major metabolite excreted in urine is FBAL which represents 57% of the administered dose.About 3% of the administered dose is excreted in urine as unchanged drug. Half Life: 45-60 minutes for capecitabine and its metabolites. Biological Half-Life The elimination half-lives of capecitabine and fluorouracil were approximately 0.75 hour. The plasma elimination half-life of capecitabine and its metabolites, including the active drug, fluorouracil, is about 45-60 minutes, except for alpha-fluoro-beta-alanine (FBAL), a catabolite of fluorouracil, which has an initial half-life of about 3 hours.
Toxicity/Toxicokinetics	Toxicity Summary Capecitabine is a prodrug that is selectively tumour-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP), within normal and tumour cells. FdUMP inhibits DNA synthesis by reducing normal thymidine production, while FUTP inhibits RNA and protein synthesis by competing with uridine triphosphate.3 The active moiety of capecitabine, fluorouracil, is cell cycle phase-specific (Sphase). Both normal and tumor cells metabolize 5-FU to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2'-deaxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, so that a deficiency of this compound can inhibit cell division. Second nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate (UTP) during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis. Hepatotoxicity Serum aminotransferase elevations occur in a proportion of patients on conventional doses of capecitabine therapy, but elevations above 5 times the upper limit of normal are uncommon, occurring in Likelihood score: E* (Unproven but suspected cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence. some have suggested a period of 24 hours before resuming nursing, although the manufacturer recommends an abstinence period of 2 weeks. Capecitabine is metabolized to fluorouracil. Limited information indicates that a maternal continuous intravenous fluorouracil infusion at a dose of 200 mg/square meter daily produces undetectable levels in milk. If capecitabine use is undertaken, monitoring of the infant's complete blood count and differential is advisable. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk. Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Plasma protein binding of capecitabine and its metabolites is less than 60% and is not concentration dependent. Capecitabine was primarily bound to human albumin (approximately 35%). Interactions Concomitant use of folic acid may affect the metabolism of capecitabine. In 4 patients receiving chronic administration of capecitabine 1250 mg/sq m twice daily with a single dose of warfarin 20 mg, the mean area under the concentration-time curve (AUC) of S-warfarin was increased by 57% and clearance was decreased by 37%. The baseline corrected AUC of INR in these patients increased by 2.8-fold, and the maximum observed mean INR increased by 91%. The mechanism for this interaction probably involves inhibition of cytochrome P-450 (CYP) 2C9 isoenzyme by capecitabine and/or its metabolites. Because the decreased rate of anticoagulant metabolism may increase patient response to coumarin and indandione derivatives, capecitabine and these agents should be used concomitantly with great caution. Leucovorin potentiates the antineoplastic activity of fluorouracil (the active drug of capecitabine) and also may increase its toxicity. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in geriatric patients receiving a weekly regimen of combination therapy with leucovorin and fluorouracil. Concomitant use of phenytoin and capecitabine may result in toxicity from increased serum phenytoin concentrations. The mechanism of interaction is presumed to be inhibition of the metabolism of phenytoin by capecitabine and/or its metabolites through inhibition of the cytochrome P-450 (CYP) 2C9 isoenzyme. In patients receiving capecitabine, serum concentrations of phenytoin must be monitored carefully, and reduction in the phenytoin dosage may be necessary. For more Interactions (Complete) data for CAPECITABINE (6 total), please visit the HSDB record page.
References	[1]. Mol Cancer Ther . 2002 Sep;1(11):923-7. [2]. Biochem Pharmacol . 1998 Apr 1;55(7):1091-7. [3]. Clin Cancer Res . 2003 Dec 1;9(16 Pt 1):6030-7.
Additional Infomation	Therapeutic Uses Antimetabolites, Antineoplastic Agent Capecitabine is indicated as a single agent for adjuvant treatment in patients with Dukes' C colon cancer who have undergone complete resection of the primary tumor when treatment with fluoropyrimidine therapy alone is preferred. Capecitabine was non-inferior to 5-fluorouracil and leucovorin (5-FU/LV) for disease-free survival (DFS). Although neither Capecitabine nor combination chemotherapy prolongs overall survival (OS), combination chemotherapy has been demonstrated to improve disease-free survival compared to 5-FU/LV. Physicians should consider these results when prescribing single-agent capecitabine in the adjuvant treatment of Dukes' C colon cancer. /Included in US product label/ Capecitabine is indicated as first-line treatment of patients with metastatic colorectal carcinoma when treatment with fluoropyrimidine therapy alone is preferred. Combination chemotherapy has shown a survival benefit compared to 5-FU/LV alone. A survival benefit over 5-FU/LV has not been demonstrated with Capecitabine monotherapy. Use of capecitabine instead of 5-FU/LV in combinations has not been adequately studied to assure safety or preservation of the survival advantage. /Included in US product label/. Capecitabine in combination with docetaxel is indicated for the treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing chemotherapy. /Included in US product label/ Capecitabine monotherapy is also indicated for the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or resistant to paclitaxel and for whom further anthracycline therapy is not indicated, eg, patients who have received cumulative doses of 400 mg/sq m of doxorubicin or doxorubicin equivalents. Resistance is defined as progressive disease while on treatment, with or without an initial response, or relapse within 6 months of completing treatment with an anthracycline-containing adjuvant regimen. /Included in US product label/ Drug Warnings Diarrhea, a dose-limiting and common adverse effect of capecitabine, occurs in 55-67% of patients receiving the drug for metastatic breast cancer or metastatic colorectal cancer, and is severe or life-threatening in 15% of patients. Nausea and vomiting occur in 43-53% and 27-37%, respectively, of patients receiving capecitabine for metastatic breast cancer or metastatic colorectal cancer. Among patients with metastatic breast cancer who developed severe nausea and/or vomiting associated with capecitabine monotherapy, onset of these adverse GI effects was early, usually occurring during the first month of treatment. Among patients receiving capecitabine alone as adjuvant therapy for stage III colon cancer, diarrhea occurred in 47% of patients and was severe or life-threatening (grade 3 or 4) in 12%; nausea occurred in 34%, and vomiting in 15%, of patients. Severe adverse GI effects associated with capecitabine may occur more frequently in geriatric patients. Among 21 patients aged 80 years or older receiving capecitabine monotherapy for metastatic breast cancer or metastatic colorectal cancer in clinical trials, severe or life-threatening (grade 3 or 4) diarrhea, nausea, or vomiting occurred in 29, 14, or 10%, respectively. Among 10 patients aged 70-80 years receiving capecitabine in combination with docetaxel for metastatic breast cancer, grade 3 or 4 diarrhea and stomatitis each occurred in 30%. Capecitabine-induced diarrhea may respond to standard antidiarrheal therapy (eg, loperamide). Patients with severe diarrhea should be closely monitored and given fluid and electrolyte replacement for dehydration as indicated. For more Drug Warnings (Complete) data for CAPECITABINE (38 total), please visit the HSDB record page. Pharmacodynamics Capecitabine is a fluoropyrimidine carbamate belonging to a group of antineoplastic agents called antimetabolites, which kill cancerous cells by interfering with DNA synthesis. It is an orally administered systemic prodrug that has little pharmacologic activity until it is converted to 5-fluorouracil (5-FU) by enzymes that are expressed in higher concentrations in many tumors. Capecitabine was designed specifically to overcome the disadvantages of 5-FU and to mimic the infusional pharmacokinetics of 5-FU without the associated complexity and complications of central venous access and infusion pumps. Particularly, since the enzymes converting 5-FU into active metabolites exist in the gastrointestinal tract, infusion of 5-FU can have gastrointestinal toxicity while also losing efficacy. Since capecitabine can be transported intact across the intestinal mucosa, it can be selectively delivered 5-FU to tumor tissues through enzymatic conversion preferentially inside tumor cells. 5-FU exerts its pharmacological action through the inhibition and interference of 3 main targets: thymidylate synthase, DNA, and RNA, leading through protein synthesis disruption and apoptosis. Population-based exposure-effect analyses demonstrated a positive association between AUC of 5-FU and grade 3-4 hyperbilirubinemia.

Solubility Data

Solubility (In Vitro)

DMSO: 72~250 mg/mL (200.4~695.7 mM) Water: ~6 mg/mL (~16.7 mM) Ethanol: ~72 mg/mL (~200.4 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 25 mg/mL (69.57 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Solubility in Formulation 5: 20 mg/mL (55.66 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7828 mL	13.9140 mL	27.8280 mL
	5 mM	0.5566 mL	2.7828 mL	5.5656 mL
	10 mM	0.2783 mL	1.3914 mL	2.7828 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.