Ubenimex-日本药典JP16

1546JP XVI

Ubenimex /Official Monographs (6)Iron <1.10>—Prepare the test solution with 1.0g of L -Tyrosine according to Method 3,and perform the test ac-cording to Method A.Prepare the control solution with 1.0mL of Standard Iron Solution (not more than 10ppm).(7)Related substances—Dissolve 0.20g of L -Tyrosine in 10mL of diluted ammonia solution (28)(1in 2),add water to make 20mL,and use this solution as the sample solution.Pipet 1mL of the sample solution,add water to make ex-actly 10mL,pipet 1mL of this solution,add water to make exactly 50mL,and use this solution as the standard solution.Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>.Spot 5m L each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography.Then develop with a mixture of 1-propanol and ammonia solution (28)(67:33)to a distance

of about 10cm,and dry the plate at 809

C for 30minutes.Spray evenly a solution of ninhydrin in a mixture of metha-nol and acetic acid (100)(97:3)(1in 100)on the plate,and then heat at 809C for 10minutes:the spot other than the principal spot obtained from the sample solution is not more intense than the spot from the standard solution.Loss on drying <2.41>Not more than 0.3z (1g,1059C,

3hours).

Residue on ignition <2.44>

Not more than 0.1z (1g).

Assay Weigh accurately about 0.18g of L -Tyrosine previ-ously dried,dissolve in 6mL of formic acid,add 50mL of

acetic acid (100),and titrate <2.50>with 0.1mol/L perchloric acid VS (potentiometric titration).Perform a blank determi-nation in the same manner,and make any necessary correc-tion.

Each mL of 0.1mol/L perchloric acid VS ＝18.12mg of C 9H 11NO 3

Containers and storage

Containers—Tight containers.

Ubenimex

ウベニメクス

C 16H 24N 2O 4:308.37

(2S )-2-[(2S ,3R )-3-Amino-2-hydroxy-4-phenylbutanoylamino]-4-methylpentanoic acid [58970-76-6]

Ubenimex,when dried,contains not less than 98.5z and not more than 101.0z of C 16H 24N 2O 4.

Description Ubenimex occurs as a white crystalline pow-der.

It is freely soluble in acetic acid (100),slightly soluble in water,and very slightly soluble in ethanol (99.5).It dissolves in 1mol/L hydrochloric acid TS.Melting point:about 2309C (with decomposition).Identification

(1)

Determine the absorption spectrum of a

solution of Ubenimex (1in 2000)as directed under Ultravio-let-visible Spectrophotometry <2.24>,and compare the spec-trum with the Reference Spectrum:both spectra exhibit simi-lar intensities of absorption at the same wavelengths.

(2)Determine the infrared absorption spectrum as di-rected in the potassium bromide disk method under Infrared Spectrophotometry <2.25>,and compare the spectrum with the Reference Spectrum:both spectra exhibit similar inten-sities of absorption at the same wave numbers.

Optical rotation <2.49>[a ]20D :－15.5–－17.59(after dry-ing,0.5g,1mol/L hydrochloric acid TS,50mL,100mm).Purity (1)Heavy metals <1.07>—Proceed with 2.0g of Ubenimex according to Method 2,and perform the test.Pre-pare the control solution with 2.0mL of Standard Lead So-lution (not more than 10ppm).

(2)Related substances—Dissolve 30mg of Ubenimex in 10mL of the mobile phase A,and use this solution as the sample solution.Pipet 2mL of the sample solution,add the mobile phase A to make exactly 200mL,and use this solu-tion as the standard solution.Perform the test with exactly 20m L each of the sample solution and standard solution as directed under Liquid Chromatography <2.01>according to the following conditions,and determine each peak area of these solutions by the automatic integration method:the area of the peak other than ubenimex obtained from the sample solution is not larger than 1/2times the peak area of ubenimex from the standard solution.Furthermore,the total area of the peaks other than ubenimex is not larger than the peak area of ubenimex from the standard solution.Operating conditions —

Detector:An ultraviolet absorption photometer (wave-length:220nm).

Column:A stainless steel column 4.6mm in inside diame-ter and 25cm in length,packed with octadecylsilanized silica gel for liquid chromatography (5m m in particle diameter).Column temperature:A constant temperature of about 259C.

Mobile phase A:A mixture of diluted 0.1mol/L potas-sium dihydrogen phosphate TS (13in 20)and acetonitrile for liquid chromatography (17:3).

Mobile phase B:A mixture of acetonitrile for liquid chro-matography and diluted 0.1mol/L potassium dihydrogen phosphate TS (13in 20)(2:1).

Flowing of the mobile phase:Control the gradient by mix-ing the mobile phases A and B as directed in the following table.

Time after injection of sample (min)

Mobile phase A

(vol z )

Mobile phase B

(vol z )

0–20100020–60100→0

0→10060–70

100

Flow rate:Adjust the flow rate so that the retention time

of ubenimex is about 14minutes.

Time span of measurement:About 5times as long as the retention time of ubenimex,beginning after the solvent peak.

System suitability —

Test for required detectability:Pipet 1mL of the standard