Determination of formaldehyde and glyoxal in varenicline tartrate using derivative method with HPLC
10.11665/j.issn.1000-5048.20210310
- VernacularTitle:衍生化HPLC法测定酒石酸伐尼克兰中甲醛和乙二醛的含量
- Author:
Yitong GUAN
1
;
Pengwei HU
;
Wenyu ZOU
;
Yuting LU
;
Min SONG
;
Taijun HANG
Author Information
1. 中国药科大学药物分析系
- Publication Type:Journal Article
- Keywords:
varenicline tartrate;
formaldehyde;
glyoxal;
genotoxic impurity;
pre-column derivatization;
HPLC
- From:
Journal of China Pharmaceutical University
2021;52(3):332-338
- CountryChina
- Language:Chinese
-
Abstract:
To establish a method for the determination of formaldehyde and glyoxal simultaneously in varenicline tartrate active pharmaceutical ingredient (API) and its intermediate, formaldehyde and glyoxal were derivatized by 2, 4-dinitrophenylhydrazine (2,4-DNPH) to improve the HPLC retention and UV detection sensitivity. Separation was performed on a C8 (150 mm × 4.6 mm, 5 μm) column by linear gradient elution using acetonitrile and water as the mobile phase; the detective wavelength was set at 380 nm.Formaldehyde and glyoxal were quantitatively determined by an external reference method.Linear calibration was established for both formaldehyde and glyoxal in the range from 0.094 to 1.88 μg/mL.The detection and the quantification limits were 0.047 μg/mL (19 μg/g) and 0.094 μg/mL (38 μg/g), respectively.The recoveries were (95.0±1.1)% and (99.4 ± 2.6)% for formaldehyde and glyoxal, respectively.This method has been fully validated to be applicable to quantitative analysis of trace amount of formaldehyde and glyoxal in varenicline tartrate API and its intermediate.Test results demonstrated that the contents of both formaldehyde and glyoxal met the permitted daily exposure (PDE) limits for the finished products of varenicline tartrate API as well as its intermediate, though the glyoxal contents in the crude intermediates were likely to exceed the limit.The established method is valuable for the manufacturing process and quality control of varenicline tartrate.
