Calcitriol

Product Overview

Calcitriol (also known as 1α,25-dihydroxycholecalciferol, 1,25-dihydroxyvitamin D₃, 1,25-DHCC) is the naturally active form of vitamin D₃ in the body, acting directly without further hepatic or renal hydroxylation — this distinguishes it from plain vitamin D₃ and alfacalcidol (the latter still requires hepatic 25-hydroxylation).

In vivo generation pathway: human vitamin D mainly relies on the conversion of 7-dehydrocholesterol in the skin to vitamin D₃ by ultraviolet irradiation. Vitamin D₃ must undergo two activation steps: ① hepatic vitamin D₃-25-hydroxylase catalyzes the formation of 25-hydroxyvitamin D₃; ② renal mitochondrial 25-hydroxyvitamin D₃-1α-hydroxylase catalyzes the formation of 1,25-(OH)₂D₃, i.e., calcitriol — this is the active form. Under physiological conditions, the daily production is approximately 0.5–1.0 μg, increasing slightly during periods of active bone synthesis (growth, pregnancy).

Why patients with kidney disease must use calcitriol (rather than plain vitamin D): patients with chronic renal failure lose renal 1α-hydroxylation capacity and cannot convert 25-(OH)D₃ into active calcitriol, leading to hypocalcemia and secondary hyperparathyroidism, which in turn cause renal osteodystrophy — supplementing plain vitamin D₃ is ineffective; the active form must be supplied directly. This is calcitriol’s core clinical positioning.

Sites of action: the two known principal sites of action are the intestine and bone: it promotes intestinal calcium transport (it is the most potent known vitamin D form for stimulating intestinal calcium absorption) and bone calcium mobilization; there is also evidence that it acts on the kidney and parathyroid glands.

The “isomer trap” that must be distinguished: calcitriol and paricalcitol (CAS 131918-61-1) have exactly the same molecular formula, C₂₇H₄₄O₃, and virtually the same molecular weight (416.64) — but calcitriol is active vitamin D₃ (cholecalciferol series), whereas paricalcitol is a 19-nor vitamin D₂ analogue (ergocalciferol series); they are two entirely different drugs. The reliable distinguishing parameter is melting point: calcitriol 119–121 ℃, paricalcitol 172–174 ℃ — a difference of more than 50 ℃. Molecular formula and molecular weight alone cannot distinguish them; the CAS number, chemical name, and melting point must be checked.

Technical Specifications

• Standards: CHP／USP／EP (USP contains a Calcitriol monograph; the marketed capsule labeling explicitly states “calcitriol, USP”; ATC codes A11CC04, D05AX03)

• Specification: 0.99 (purity ≥99.0%, HPLC); reagent/reference grades commonly >95% (HPLC, TRC), >97% (HPLC, TCI), ≥99% (HPLC, Tocris), HPLC ≥98% (analytical standard)

• CAS No.: 32222-06-3 (EINECS 250-963-8; UNII FXC9231JVH; MDL MFCD00867079; BRN 7559394; Merck Index 14,1644; RTECS FZ4645000; PubChem CID 5280453; KEGG; DrugBank)

• Molecular formula: C₂₇H₄₄O₃

• Molecular weight: 416.64 (consistent across ChemicalBook, 化工百科, Baidu Baike, and Sigma-derived pages; PubChem calculated value 416.6; MOLBASE 416.645; 416.637 also reported); exact mass depends on isotopic composition

• Appearance: white to off-white crystalline powder (white crystalline powder); other sources describe it as a colorless, crystalline solid; USP describes it as white to almost white crystals

• Purity (HPLC): ≥ 99.0%

• Melting point: 119–121 ℃ (consistent across ChemicalBook, 化工百科, MOLBASE, Baidu Baike, Huzhen Bio, Yuanye, and other sources; recommended value). This is a key identification point: it contrasts sharply with paricalcitol (melting point 172–174 ℃), which shares the same molecular formula, enabling rapid differentiation of the two substances. The above values come from literature/supplier standards, not from a publicly verifiable official pharmacopoeial melting point (the USP monograph labeling does not list a melting point)

• Specific optical rotation: [α]D²⁵ +48° (methanol) (consistent across ChemicalBook, 化工百科, MOLBASE, Huzhen Bio, and other sources); MOLBASE additionally records “Specific optical rotation = +48 deg at 22 °C/D (methanol)” — the measurement temperature is stated as either 22 ℃ or 25 ℃ with the same value; the conditions should be noted when quoting

• Chemical name: 9,10-secocholesta-5,7,10(19)-triene-1α,3β,25-triol; i.e., (5Z,7E)-(1S,3R)-9,10-secocholesta-5,7,10(19)-triene-1,3,25-triol; also known as 1α,25-dihydroxycholecalciferol, 1,25-dihydroxyvitamin D₃

• Stereochemistry: multiple defined stereocenters (1S/1α, 3R/3β, 5Z, 7E, etc.) on a seco-steroid skeleton; note: some databases give two InChIKey notations (GMRQFYUYWCNGIN-NKMMMXOESA-N and GMRQFYUYWCNGIN-UNVJKIGWSA-N), arising from different stereolayer annotation conventions — the stereochemical description must be checked when quoting

• Solubility: practically insoluble in water (aqueous solubility approx. 7.9×10⁻⁴ mg/L at 25 ℃, estimated; H₂O <1 mg/mL); soluble in DMSO (approx. 50 mg/mL; another source records 240 mg/mL) and ethanol (soluble, approx. 77 mg/mL); soluble in other organic solvents — USP explicitly states “soluble in organic solvents; practically insoluble in water”

• UV absorption maximum (λmax): 265 nm (lit.) — the characteristic absorption of the triene structure of the vitamin D series, and an important parameter for assay and identification of this product

• Acid dissociation constant (pKa): 14.43 ± 0.40 (calculated)

• Calculated physicochemical parameters: density approx. 1.0362 (estimated; also recorded as 1.1 ± 0.1); boiling point approx. 474.91 ℃ (estimated; also recorded as 565.0 ± 50.0 ℃ at 760 mmHg); refractive index approx. 1.4700 (estimated); flash point approx. 14 ℃; vapor pressure approx. 1.2×10⁻¹² mmHg (25 ℃, estimated); LogP approx. 5.1; topological polar surface area approx. 60.7 Ų; hydrogen bond donors 3／acceptors 3; rotatable bonds 6; heavy atom count 30; BCS class 2/4

• Stability: sensitive to air and light (Air and Light Sensitive); degrades under prolonged light exposure; unstable in solution — prepare fresh before use; some sources state “keep away from direct sunlight, store under nitrogen”

• Marketed dosage forms: capsules 0.25 μg, 0.5 μg; injection 1 μg/mL, 2 μg/mL; ointment (3 μg/g, for psoriasis); capsules contain BHA and BHT as antioxidants

• Storage conditions: store sealed at 2–8 ℃ (ChemicalBook, Sigma-derived pages); some sources recommend −20 ℃ (Yuanye, TargetMol); must be protected from light, blanketed with nitrogen, and protected from air oxidation; unstable in solution — prepare immediately before use

Applications

• Renal osteodystrophy and hypocalcemia in chronic renal failure (especially dialysis patients) (core indication): for hypocalcemia and renal bone disease in patients on chronic renal dialysis — because renal failure patients lose 1α-hydroxylation capacity, the active form must be supplied directly. This is calcitriol’s most irreplaceable clinical value

• Hypoparathyroidism and pseudohypoparathyroidism: for hypocalcemia due to postsurgical, idiopathic, or pseudo-hypoparathyroidism

• Rickets and osteomalacia: for vitamin D-dependent rickets (pseudo-vitamin D-deficiency rickets) and hypophosphatemic vitamin D-resistant rickets, among others

• Postmenopausal and senile osteoporosis: for promoting intestinal calcium absorption and improving calcium balance

• Psoriasis (topical): the ointment formulation is used for mild-to-moderate plaque psoriasis (ATC D05AX03), acting by inhibiting keratinocyte proliferation and promoting their differentiation — note: paricalcitol is administered by injection/orally for hyperparathyroidism, whereas calcitriol ointment is a topical dermatological preparation; the two differ in both indication and route of administration

• Pharmacology and mechanism research: used in studies of vitamin D receptor (VDR) binding and activation, intestinal calcium transport and calbindin expression, bone metabolism and mineralization, immunomodulation (the literature reports it as a potent inhibitor of PHA-induced lymphocyte proliferation, inhibiting approx. 70% of tritiated thymidine incorporation after 72 hours of culture), cell differentiation, and antiproliferation

• Formulation and manufacturing: used in formulation development of soft capsules, injections (containing polysorbate 20, sodium ascorbate, disodium EDTA, and a phosphate buffer system under nitrogen), and ointments; the API is extremely sensitive to air and light and unstable in solution — the entire manufacturing process must strictly control light protection, nitrogen blanketing, low temperature, and immediate use after preparation, and closely monitor related substances (the vitamin D series is prone to isomerization, oxidation, and triene-structure degradation); capsule formulations require antioxidants (BHA／BHT) with fractionated coconut oil triglycerides as the vehicle; attention must also be paid to identity differentiation from paricalcitol (same molecular formula and molecular weight) — multiple identification by melting point (119–121 ℃), specific rotation (+48°), λmax (265 nm), and chiral chromatography is recommended; suitable for analytical method development and validation, stability studies, and GMP scale-up and CMO／CDMO contract manufacturing

Safety notice: This product is an active pharmaceutical ingredient (API) intended only for legitimate industrial, research, and pharmaceutical manufacturing use; it is not for end-user clinical use or self-medication guidance. The finished product is a prescription drug that must be prescribed by a physician with regular monitoring of serum calcium, serum phosphate, calcium-phosphate product, and renal function. Key warnings: ① Hypercalcemia — the core risk of vitamin D agents, which can lead to hypercalcemic crisis, ectopic calcification, and deterioration of renal function; the risk increases significantly with concomitant calcium preparations, thiazide diuretics, or high-dose vitamin D — reduce the dose or discontinue immediately if hypercalcemia occurs; ② Digitalis interaction — hypercalcemia induced by calcitriol can precipitate digitalis toxicity (arrhythmias); with concomitant use, serum calcium and ECG must be closely monitored and the digitalis dose adjusted as appropriate; ③ Magnesium-containing preparations (antacids) — concomitant use of magnesium-containing antacids in chronically dialyzed patients may cause hypermagnesemia; ④ Aluminum preparations — long-term concomitant use with aluminum-containing phosphate binders may increase aluminum accumulation toxicity; ⑤ Ketoconazole — may inhibit calcitriol synthase, reducing its endogenous production; ⑥ Bile acid sequestrants and mineral oil — may reduce intestinal absorption. Contraindications: hypercalcemia, vitamin D intoxication, known hypersensitivity to this product. Adverse reactions: manifestations related to hypercalcemia (anorexia, nausea, vomiting, constipation, polyuria, polydipsia, muscle weakness, confusion), headache, abdominal pain; long-term overdose may cause soft-tissue and vascular calcification, nephrolithiasis, and renal impairment. Overdose management: discontinue the drug, institute a low-calcium diet and adequate hydration; loop diuretics, glucocorticoids, or calcitonin may be used if necessary; because of high protein binding, hemodialysis clearance is limited. Special populations: in pregnancy and lactation, the physician must weigh benefits against risks (FDA pregnancy category C); in children, dosing must be individualized by body weight/body surface area. API handling warning: this product is a highly potent steroid compound extremely sensitive to air and light, GHS-classified as acute oral/dermal/inhalation toxicity category 1–2 and specific target organ toxicity (repeated exposure) category 1 (H300+H310+H330, H372), signal word “Danger”, hazard symbols T+／Xn／F, dangerous goods transport number UN 2811 (6.1/PG I), WGK Germany 3; the literature records a mouse intraperitoneal LD50 of approx. 1.9 mg/kg. Handling must be performed in a fume hood with protective gloves, protective clothing, respiratory and eye/face protection, full light protection (amber containers), and nitrogen blanketing; avoid dust inhalation and skin contact; ingestion is strictly prohibited. Store sealed and protected from light at 2–8 ℃ (some recommend −20 ℃). It must be strictly distinguished from paricalcitol (CAS 131918-61-1) — the two share the same molecular formula and molecular weight but are different drugs, and mix-ups can cause serious medication errors.

Product information: please contact us. This information is for reference only.