Phân tích tạp chất - Kiểm nghiệm thuốc - Esomeprazole

Kiểm nghiệm tạp chất esomeprazole tổng hợp - Chương trình đào tạo Dược sĩ Đại học Năm 5 - ĐH Y Dược TPHCM

PHARMACEUTICAL IMPURITIES TESTING

ESOMEPRAZOLE

GROU

P 1

» Brand name: Nexium® -AstraZeneca and

Nexium® OTC- Pfizer

» Ranking 18th (Nexium®) in top 50 pharmaceutical products by global sales (2014) 1

http://www.pmlive.com/top_pharma_list/Top_50_pharmaceutical_products

IC

5 QUALIFICATION & IMPURITY TEST

Let’s go with the second set of slides

the important

thing is to never stop questioning”

“

-Albert

Einstein-IMPURITIE S

Esomeprazole impurities include A, B, C, D, E, F and S-binol

ESOMEPRAZOLE IMPURITIES

ESOMEPRAZOLE IMPURITIES

ESOMEPRAZOLE IMPURITIES

Impurity S-binol

1-(2-Hydroxynaphthalen-1-yl)naphthalene-2-ol

IMPURITY

ORIGIN

Imp-E is degradent Imp-D and Imp-C are process

impurities as well as degradents Imp-A, Imp-B and S-binol are process impurities

Impurity C Impurity D

Journal of Pharmaceutical and

Biomedical Analysis 57 (2012), 109-114

SOURCES OF ESOMEPRAZOLE IMPURITIES

PROCESS IMPURITIES

Omeprazole (Racemic)

Esomeprazol

e (S) Impurity F

optical resolution agent or

asymmetrica lly oxidizing

ENANTIOMER PURITY

Patent WO2008102145A2

Patent WO 2007/013743 A1

PROCESS IMPURITIES

(S)-binol is an optical

resolution agent  

Impurity S-binol

Method of preparing Esomeprazole and salts thereof,

Patent WO 2007/013743 A1

Oxi dat

ion

GHS classification, toxicity in humans, damage to patients

GHS CLASSIFICATION

Globally Harmonized System

Impurities A B C D E F S GHS hazard statements EXPLAIN

Health hazards

Toxic if swallowed

H303 X May be harmful if swallowed

H315 X X X X X X Causes skin irritation

H317 X X X X May cause an allergic skin reaction

H319 X X X X X X X Causes serious eye irritation

H335 X X X X X X May cause respiratory irritation

H402 X

Environmental hazards

Harmful to aquatic lifeH410 X Very toxic to aquatic life with long-lasting effectsH411 X Toxic to aquatic life with long-lasting effectsH412 X X Harmful to aquatic life with long-lasting effects

Esomeprazole Magnesium

Dihydrate Esomeprazole Magnesium

Tetrahydrate and Anhydrous

PRODUCT

Esomeprazole Magnesium

Delayed-release Capsule

MONOGRAPHS

Esomeprazole Magnesium

Trihydrate

MONOGRAPHS

MATERIAL IMPURITY CRITERION

MATERIAL IMPURITY USP 40 BP 2016 EP 8.0

Esomeprazole

Magnesium

Dihydrate

unspecified impurityImpurity DImpurity E

MATERIAL IMPURITY CRITERION

MATERIAL IMPURITY USP 40 BP 2016 EP 8.0

Esomeprazole

Magnesium

Anhydrous

unspecified impurityImpurity DImpurity E

-IMPURITIES CRITERION IN PRODUCTS

PRODUCT IMPURITY USP 40 BP 2016 EP 8.0

-Total NMT

-RELATED IMPURITY TESTING METHOD

Esomeprazole Magnesium

Octylsilyl silica gel for

Acetonitrile + phosphate buffer pH 7.6

Acetonitrile + phosphate buffer pH7.6

Acetonitrile R+phosphate buffer

of esomeprazole

4 times the retention time of esomeprazole

RELATED IMPURITY TESTING METHOD

Esomeprazole Magnesium

Column 4.6-mm × 15-cm; 5-µm

4.0-mm × 12.5-cm or 4.6-

ENANTIOMER IMPURITY TESTING

Method LC LC LC

Stationary

phase

Packing L41 (Immobilized α1- acid glycoprotein on spherical silica particles) 5 μm

Packing L7 L41 (Immobilized α1-acid glycoprotein on spherical silica particles)

α1-acid-glycoprotein silica gel for chiral separation R

5 μm

Mobile

phase

Acetonitrile and phosphate buffer pH 6.5

Acetonitrile and phosphate buffer

Acetonitrile R and phosphate buffer

RELATED IMPURITY TESTING METHOD

4.0-mm × 10-cm ; 5-µm

Flow rate 0.8 mL/min 0.6 mL/min 0.6 mL/min

The Universe in a Nutshell

F binol

S-DƯỢC ĐIỂN VIỆT NAM IV

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