Piperaquine phosphate is a bisquinoline antimalarial drug that may be utilized in combination with artemisinin in antimalarial research.

Physicochemical Properties

Molecular Formula	C29H35CL2N6O4P
Molecular Weight	633.51
Exact Mass	632.183
CAS #	85547-56-4
Related CAS #	Piperaquine tetraphosphate tetrahydrate;915967-82-7;Piperaquine tetraphosphate;911061-10-4;Piperaquine-d6 tetraphosphate;Piperaquine;4085-31-8
PubChem CID	174478
Appearance	Off-white to light yellow solid powder
Boiling Point	721.1ºC at 760mmHg
Flash Point	389.9ºC
LogP	4.501
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	6
Heavy Atom Count	42
Complexity	704
Defined Atom Stereocenter Count	0
SMILES	OP(=O)(O)O.ClC1C=CC2=C(N3CCN(CCCN4CCN(C5C=CN=C6C=C(C=CC=56)Cl)CC4)CC3)C=CN=C2C=1
InChi Key	KATNPMSTHHZOTK-UHFFFAOYSA-N
InChi Code	InChI=1S/C29H32Cl2N6.H3O4P/c30-22-2-4-24-26(20-22)32-8-6-28(24)36-16-12-34(13-17-36)10-1-11-35-14-18-37(19-15-35)29-7-9-33-27-21-23(31)3-5-25(27)29;1-5(2,3)4/h2-9,20-21H,1,10-19H2;(H3,1,2,3,4)
Chemical Name	7-chloro-4-[4-[3-[4-(7-chloroquinolin-4-yl)piperazin-1-yl]propyl]piperazin-1-yl]quinoline;phosphoric acid
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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

ln Vivo	In mice, piperaquine (10-90 mg/kg; single ip) reduces parasitemia at all tested doses[1]. In mice with malaria, piperaquine (90 mg/kg; single ip) shows the following characteristics: in healthy mice, the t1/2, apparent clearance, and apparent volume of distribution are 17.8 days, 33.5 mg·h/L, 1.55 L/h/kg, and 956 L/kg, respectively, whereas in infected mice, they are 16.1 days, 27.3 mg·h/L, 1.9 L/h/kg, and 1,059 L/kg[1].
Animal Protocol	Animal/Disease Models: Male balb/c (Bagg ALBino) mouse: (7 to 8 weeks) are inoculated with Plasmodium berghei parasites[1] Doses: 0, 10, 30, 90 mg/kg Route of Administration: A single ip administration Experimental Results: The median survival time was 10 days at dose of 10 mg/kg. The median survival time was 54 days at dose of 30 mg/ kg. All mice were active and alert and had stable body weights throughout the course of the study at dose of 90 mg/kg. Animal/Disease Models: Male Swiss mice (6 weeks old)[1] Doses: 90 mg/kg (pharmacokinetic/PK Analysis ) Route of Administration: A single ip administration Experimental Results: t1/2=17.8 d; AUC=33.5 mg·h/L; apparent clearance=1.55 L/h/kg; apparent volume of distribution=956 L/kg.
References	[1]. Moore BR, et, al. Pharmacokinetics and pharmacodynamics of piperaquine in a murine malaria model. Antimicrob Agents Chemother. 2008 Jan; 52(1): 306-11. [2]. Davis TME, et, al. Piperaquine: a resurgent antimalarial drug. Drugs. 2005; 65(1): 75-87.

Solubility Data

Solubility (In Vitro)

H2O : 17.86 mg/mL (28.19 mM)

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.5785 mL	7.8925 mL	15.7851 mL
	5 mM	0.3157 mL	1.5785 mL	3.1570 mL
	10 mM	0.1579 mL	0.7893 mL	1.5785 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.