The US administration of President Joe Biden announced sanctions Tuesday against 25 individuals and entities based in China, alongside three other parties in Canada.
Eight indictments charging China-based chemical manufacturing firms and staff were also issued, with Attorney General Merrick Garland saying the global supply chain of fentanyl "often starts... in China".
Beijing hit back at Washington Wednesday, saying the Chinese government is "among the first around the world to regulate substances like fentanyl".
"We firmly oppose the United States' sanction and prosecution against Chinese entities and individuals, and the severe infringement of the lawful rights and interests of the relevant enterprises and persons," Beijing's foreign ministry told AFP.
"The Chinese government has been strictly cracking down on drug crimes... and we deploy the harshest control on precursor chemicals," it said.
"The fentanyl crisis in the United States is rooted in the country itself."
The ministry added that "solemn representations" have been lodged against the United States.
"Imposing pressure and sanctions cannot solve the United States' own problems. It will only create obstacles in the China-US cooperation on drug control," it said.
- Chinese 'syndicate' -
Biden's administration has made the fight against fentanyl a priority, with the synthetic opioid blamed for tens of thousands of deaths in recent years.
Tuesday's actions are aimed at exposing and disrupting a network "responsible for manufacturing and distributing illicit drugs", according to Deputy Treasury Secretary Wally Adeyemo.
The China-based network is "responsible for the manufacturing and distribution of ton quantities of fentanyl, methamphetamine, and MDMA precursors", said Treasury.
It is the "source of supply" for many US-based narcotics traffickers, dark web vendors, virtual currency money launderers and Mexico-based criminal organisations, it added.
The parties designated are also allegedly involved in trafficking xylazine -- a veterinary sedative known as "tranq" -- and nitazenes, which are often mixed with fentanyl or other drugs and pose a higher risk of fatal overdoses.
Among the individuals designated Tuesday by the Treasury are Wang Shucheng and Du Changgen -- members of a Chinese "syndicate" -- as well as their affiliates.
Wang was said to have directed others to establish companies used as cover to move pharmaceutical goods globally, while Du maintains the most influence over the organisation.
"Du Changgen and persons operating under him have been responsible for approximately 900 kilograms of seized fentanyl and methamphetamine precursors shipped to the United States and Mexico," the department said.
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