ZOLEDRONIC ACID

ZOLEDRONIC ACID

PRODUCT IDENTIFICATION

CAS NO.

118072-93-8

ZOLEDRONIC ACID

EINECS NO.

FORMULA C₅H₁₀N₂O₇P₂·H₂O

MOL WT. 290.10

H.S. CODE

2931.00.9999

TOXICITY

SYNONYMS Zometa®; Aclasta; Zoledronate;

(1-Hydroxy-2-imidazol-1-yl-phosphonoethyl) phosphonic acid monohydrate;

SMILES

c1cncn1CC(O)(P(O)(=O)O)P(O)(=O)O

CLASSIFICATION

BONE DENSITY REGULATORS / Phosphonates

PHYSICAL AND CHEMICAL PROPERTIES

PHYSICAL STATE white crystalline powder

MELTING POINT

BOILING POINT

SPECIFIC GRAVITY

SOLUBILITY IN WATER sparingly soluble

pH 2 (0.7% solution)

VAPOR DENSITY

AUTOIGNITION

NFPA RATINGS

REFRACTIVE INDEX

FLASH POINT

STABILITY

Stable under ordinary conditions.

APPLICATIONS

Zoledronate is the most potent inhibitor of osteoclastic bone resorption due to the presence of the imidazole side chain. The inhibition of osteoclast activity resulting in the normalization of serum calcium level is the major pharmacologic application of bisphosphonates. Zoledronic acid is a white crystalline powder; highly soluble in sodium hydroxide solution; sparingly soluble in water; insoluble in organic solvents. The chemical designation is [1-hydroxy-(1H-imidazol-1-yl)-phosphonoethyl] phosphonic acid.

Biphosphonate, a salt, ester, or anion of a dimer of phosphonic acid (diphosphonic acid), inhibits bone resorption as a sodium salt and complexed with technetium Tc 99m for bone imaging. The monophosphonates are not active. Biphosphonates are used in disorders affecting the skeleton such as osteoporosis, metastatic disease, and Paget's disease. While bisphosphonates are analogues of endogenous pyrophosphate structurally, they are characterized by a P-C-P bond, the linking oxygen is replaced with a carbon, which is resistant to enzymatic and chemical hydrolysis. General structure is

Bisphosphonate

Side chains are responsible for chemical-physicla properties, mechanism of resorption, and pharmacokinetics. It is known that biphosphonates bind strongly to hydroxyapatite crystals at the sites of increased bone turnover preferentially and inhibit the formation, aggregation, and dissolution of the crystals. They also may inhibit osteoclast function directly, promotion of osteoclast apoptosis, and interference with osteoblast-mediated osteoclast activation.
Bisphosphonate products include: (see below)

Etidronic acid (CAS #: 2809-21-4)
Clodronic acid (CAS #: 10596-23-3)
Tiludronic acid (CAS #: 89987-06-4)
Medronic acid (CAS #: 1984-15-2)
Pamidronic acid (CAS #: 40391-99-9)
Neridronic acid (CAS #: 79778-41-9)
Olpadronic acid (CAS #: 63132-39-8)
Alendronic acid (CAS #: 66376-36-1)
Ibandronic acid (CAS #: 114084-78-5)
Risedronic acid (CAS #: 105462-24-6)
Zoledronic Acid (CAS #: 118072-93-8)

Medication members for the treatment of postmenopausal osteoporosis in women by building healthy bone and restoring some of the bone loss as a result of osteoporosis include vitamin D and calcium supplements, bisphosphonate drugs, certain selective estrogen receptor modulators, estrogen replacements and parathyroid hormones. Examples are below:

Bone Density Regulators	CAS RN
Alendronate sodium	121268-17-5
Alendronic acid	66376-36-1
Calcifediol	63283-36-3
Calcitonin	47931-85-1
Calcitriol	32222-06-3
Cholecalciferol	67-97-0
Clodronic acid	10596-23-3
Dihydrotachysterol	67-96-9
Disodium cycloheptylaminomethylenediphosphonate	138330-18-4
Ergocalciferol	50-14-6
Etidronate Disodium	7414-83-7
Etidronic acid	2809-21-4
Gallium nitrate	135886-70-3
Hydroxycholecalciferols
Ibandronate sodium hydrate	138926-19-9
Ibandronic acid	114084-78-5
Olpadronic acid	63132-39-8
Oxidronic acid	15468-10-7
Pamidronate disodium	109552-15-0
Pamidronic acid disodium salt	57248-88-1
Pamidronic acid	40391-99-9
Potassium phosphate dibasic	7758-11-4
Procalcitonin	56645-65-9
Raloxifene	84449-90-1
Risedronate sodium	115436-72-1
Risedronic acid	105462-24-6
Secalciferol	55721-11-4
Tamoxifen	10540-29-1
Teriparatide	52232-67-4
Tiludronic acid	89987-06-4
Toremifene citrate	89778-27-8
Toremifene	89778-26-7
Vitamin D	1406-16-2
Vitamin D2 sulfate	1784-46-9
Zoledronic acid	118072-93-8
24,25-Dihydroxyvitamin D 3	40013-87-4
25-Hydroxyvitamin D 2	21343-40-8

SALES SPECIFICATION

APPEARANCE

white crystalline powder

ASSAY

99.0% min (on dry basis)

RELATED SUBSTANCE

0.5% max

HEAVY METALS

10ppm max

CLARITY OF SOLUTION

clear and colorless

TRANSPORTATION

PACKING

HAZARD CLASS

UN NO.

OTHER INFORMATION

European Hazard Symbols: XI, Risk Phrases:36/37/38, Safety Phrases:26-36

BISPHOSPHONATE PRODUCTS

Biphosphonate (Sosium salt)	CAS #	Side Chains (R1, R2)	STRUCTURE
Alendronic acid (Alendronate)	66376-36-1	R1= -OH R2= -C₃H₆NH₂
Clodronic acid (Clodronate)	10596-23-3	R1= -Cl R2= -Cl
Etidronic acid (Etidronate)	2809-21-4	R1= -OH R2= -CH₃
Ibandronic acid (Ibandronate)	114084-78-5	R1= -OH R2= -C₂H₄N(CH₃)C₅H₁₁
Medronic acid (Medronate)	1984-15-2	R1= -H R2= -H
Neridronic acid (Neridronate)	79778-41-9	R1= -OH R2= -C₅H₁₀NH₂
Olpadronic acid (Olpadronate)	63132-39-8	R1= -OH R2= -C₂H₄N(CH₃)₂
Pamidronic acid (Pamidronate)	40391-99-9	R1= -OH R2= -C₂H₄NH₂
Risedronic acid (Risedronate)	105462-24-6	R1= -OH R2=
Tiludronic acid (Tiludronate)	89987-06-4	R1= -H R2= -S-CH₄Cl
Zoledronic Acid (Zoldronate)	118072-93-8	R1= -OH R2=

PRICE INFORMATION