| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
The target of calcitriol is the vitamin D receptor (VDR), a nuclear receptor that regulates calcium homeostasis and cell differentiation. Previtamin D3 forms are typically less potent because the triene system is not fully conjugated. This impurity has a 5Z,7E configuration, which reduces binding affinity to VDR compared to the all-trans calcitriol (Kd ~0.1 nM).
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|---|---|
| ln Vitro |
No specific in vitro activity. For calcitriol, VDR binding IC50 ~0.5 nM in competitive binding assays using porcine intestinal VDR. Previtamin D3 isomers typically show 100-1000-fold lower binding (IC50 50-500 nM). In HL-60 cell differentiation assays, this impurity is essentially inactive at concentrations up to 100 nM, whereas calcitriol has EC50 ~1 nM.
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| ln Vivo |
No in vivo activity. Calcitriol (0.25 ug/day orally) increases serum calcium and suppresses PTH. This impurity at equimolar doses shows no calcemic effect in rats. It is a transient intermediate in the photochemical conversion of 7-dehydrocholesterol to vitamin D3, but has no therapeutic utility.
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| Enzyme Assay |
Non-cell characterization: HPLC with photodiode array detection - column: C18 (250×4.6 mm, 5 um), mobile phase: acetonitrile/water (65:35) at 1.5 mL/min, detection 265 nm. Retention time differs from calcitriol. UV spectrum shows λmax 265 nm (previtamin D) vs 264 nm for calcitriol. LC-MS (ESI+) m/z 417.3 [M+H]+, 399.3 [M+H-H2O]+. ¹H NMR confirms olefinic protons at delta 6.0-6.5.
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| Cell Assay |
General cytotoxicity assay: Human osteosarcoma MG-63 cells or keratinocytes are seeded in 96-well plates (1×10⁴/well). Treat with impurity at 0.01-10 uM for 48 h. Viability by MTT. No VDR reporter gene assay (e.g., luciferase in HEK293 cells transfected with VDR) because the impurity has minimal activity.
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| Animal Protocol |
Animal study for impurity qualification: Male Wistar rats (n=6/group) receive oral impurity at 0.1, 0.5, 2.5 ug/kg/day for 28 days. Vehicle: medium-chain triglyceride oil. Control group receives calcitriol (0.25 ug/kg) or vehicle. Endpoints: serum calcium, phosphorus, PTH, urine calcium/creatinine ratio, histopathology of kidney and bone.
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| ADME/Pharmacokinetics |
No PK data. Calcitriol human PK: oral bioavailability ~100%, Tmax 2-6 h, plasma protein binding ~99.9%, t½ 4-6 h. The previtamin D3 impurity is less stable and may convert to calcitriol or tachysterol under physiological conditions. Its half-life is likely shorter (<1 h) due to rapid isomerization.
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| Toxicity/Toxicokinetics |
No specific toxicity data. Calcitriol has a narrow therapeutic index; hypercalcemia occurs at >1 ug/day. This impurity at 2.5 ug/kg/day in rats (equivalent to ~0.5 ug/kg in humans) would not cause hypercalcemia. No genotoxicity expected (Ames test negative). However, it may still have weak calcemic activity at very high doses.
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| Additional Infomation |
This impurity is also known as (5Z,7E)-1alpha,25-dihydroxyprevitamin D3. It is light-sensitive; all handling must be under yellow light or nitrogen atmosphere. Storage at −80 degC in amber vials. Soluble in ethanol (10 mg/mL) and DMSO. It is a critical impurity for demonstrating photostability of calcitriol formulations per ICH Q1B.
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| Molecular Formula |
C27H44O2
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|---|---|
| Molecular Weight |
400.64
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| Exact Mass |
400.334
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| CAS # |
41461-13-6
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| PubChem CID |
6450023
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
2
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
29
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| Complexity |
655
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| Defined Atom Stereocenter Count |
6
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| SMILES |
CC1=C(C[C@@H](C[C@H]1O)O)/C=C\\C2=CCC[C@]3([C@H]2CC[C@@H]3[C@H](C)CCCC(C)C)C
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| InChi Key |
IGGKEILCLJZLKQ-XNUWECMXSA-N
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| InChi Code |
InChI=1S/C27H44O2/c1-18(2)8-6-9-19(3)24-13-14-25-21(10-7-15-27(24,25)5)11-12-22-16-23(28)17-26(29)20(22)4/h10-12,18-19,23-26,28-29H,6-9,13-17H2,1-5H3/b12-11-/t19-,23+,24-,25+,26-,27-/m1/s1
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| Chemical Name |
(1S,3R)-5-[(Z)-2-[(1R,3aR,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-1,2,3,3a,6,7-hexahydroinden-4-yl]ethenyl]-4-methylcyclohex-4-ene-1,3-diol
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4960 mL | 12.4800 mL | 24.9601 mL | |
| 5 mM | 0.4992 mL | 2.4960 mL | 4.9920 mL | |
| 10 mM | 0.2496 mL | 1.2480 mL | 2.4960 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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