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Determination of bis(2-chloroethyl)amine hydrochloride and 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride in trazodone hydrochloride by UPLC-MS/MS
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Jun-yue WAN1, Hua CHEN2, *, Jie YIN2, *
Acta Pharmaceutica Sinica | 2021, 56(5) : 1439 - 1443
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Acta Pharmaceutica Sinica | 2021, 56(5): 1439-1443
Original Articles
Determination of bis(2-chloroethyl)amine hydrochloride and 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride in trazodone hydrochloride by UPLC-MS/MS
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Jun-yue WAN1, Hua CHEN2, *, Jie YIN2, *
Affiliations
  • 1. China Pharmaceutical University, Nanjing 210000, China
  • 2. NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs, National Institutes for Food and Drug Control, Beijing 100050, China
Published: 2021-05-12 doi: 10.16438/j.0513-4870.2020-1937
Outline
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An UPLC-MS/MS method was established for the quantification of the genotoxic impurities bis(2-chloroethyl)amine hydrochloride and 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride in trazodone hydrochloride. The chromatographic separation of the two genotoxic impurities was performed on Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 μm) at 20℃. A mixture of 5 mmol·L-1 ammonium hydrogen carbonate aqueous solution and acetonitrile at a flow rate of 0.3 mL·min-1 in gradient elution mode was employed as mobile phase. The UPLC-MS/MS was equipped with electrospray ionization in positive ionization mode and adopted multiple reaction monitoring mode. We found that the calibration curves of the two genotoxic impurities were linear in the range of 0.1-10 ng·mL-1. The limit of detection was 0.10 ng·mL-1 for bis(2-chloroethyl)amine hydrochloride and the average recovery was 101.53% (RSD=4.06%). The limit of detection was 0.01 ng·mL-1 for 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride and the average recovery was 97.95% (RSD=1.27%). The sample solution was stable for 24 h. No bis(2-chloroethyl)amine hydrochloride was detected in the samples, and the content of 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride in the samples was within the limit. This research provides a method to improve the quality control standards of trazadone.

UPLC-MS/MS  /  trazodone hydrochloride  /  genotoxic impurity  /  bis(2-chloroethyl)amine hydrochloride  /  1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride
Jun-yue WAN, Hua CHEN, Jie YIN. Determination of bis(2-chloroethyl)amine hydrochloride and 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride in trazodone hydrochloride by UPLC-MS/MS[J]. Acta Pharmaceutica Sinica, 2021 , 56 (5) : 1439 -1443 . DOI: 10.16438/j.0513-4870.2020-1937
Year 2021 volume 56 Issue 5
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Article Info
doi: 10.16438/j.0513-4870.2020-1937
  • Receive Date:2020-12-20
  • Online Date:2025-12-18
  • Published:2021-05-12
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History
  • Received:2020-12-20
  • Revised:2021-03-28
Affiliations
    1. China Pharmaceutical University, Nanjing 210000, China
    2. NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs, National Institutes for Food and Drug Control, Beijing 100050, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
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Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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