The EU on Friday agreed to sanction President Bashar al-Assad's British-born wife Asma, along with his mother, sister and sister-in-law as the bloc tightened the noose on the Syrian regime.
Diplomats said European Union foreign ministers gathered in Brussels had agreed an assets freeze and travel ban on "Assad's wife, mother, sister and sister-in-law", and eight other members of his entourage.
Joining the talks, British Foreign Secretary William Hague said "it's important that we tighten the diplomatic and economic stranglehold" on the Syrian regime.
"Their behaviour continues to be murdering and totally unacceptable in the eyes of the world," Hague said.
The EU must pile on the pressure "with sanctions which I hope will cover not only members of the regime but people associated closely with the regime," he added.
The names of the 12 individuals and two firms targeted will be published in the EU Official Journal on Saturday, when the sanctions take effect.
"Everybody has to know, the regime, the entourage of the regime, the clan of the regime, that we are being serious," said German Foreign Minister Guido Westerwelle. "The clan of the regime of Assad has to be included."
The Syrian first lady, a Western-educated former banker and style icon, is a British national, however, and in London officials said an EU travel ban could not prevent her from entering Britain.
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"British citizens subject to EU travel bans cannot be refused entry to the UK," said a UK Border Agency spokesperson.
But the ban would stop her from travelling to the other 26 EU nations, an EU diplomat said.
It was widely believed Asma al-Assad's grounding in Western values would help give the regime a more human face and shatter the isolation of the secretive Assad family.
But in the last weeks the first lady dubbed a "rose in the desert" by Vogue became the focus of sharp criticism after Britain's Guardian newspaper released e-mails showing the ruling couple shopping for luxury goods as the country slid into bloody chaos.
The glamorous mother of three, pictured in designer outfits and Christian Louboutin shoes, has often been compared to the likes of Queen Rania of Jordan or France's Carla Bruni, with a reported fondness for Chanel in particular.
Tall, stylish and charismatic, her impeccable British accent and credentials long helped promote the soft side of an iron-fisted regime.
The latest sanctions are the 13th round against the Assad regime, including oil and arms embargoes in response to a crackdown that has left more than 9,000 people dead in a revolt that began as peaceful protests.
Assad himself was targeted by EU restrictive measures as far back as May.
Threatening further sanctions in coming days, Swedish Foreign Minister Carl Bildt said the measures aimed to send "a very powerful signal to everyone in the regime that the killing has to stop, the violence has to stop, there has to be dialogue, there has to be a political process."
"That is the only way to prevent the country from descending into sectarian civil war that would have devastating consequences."