THERESA May’s premiership is in its final days after ministers urged her to quit and she lost yet another Cabinet minister over Brexit with the departure of Andrea Leadsom.

The Commons Leader said she was resigning with a “heavy heart” but could not support the Prime Minister’s new plan, which includes votes on a second EU referendum and a temporary customs union.

"I no longer believe our approach will deliver on the referendum result," she declared.

It was Mrs Leadsom’s decision to pull out of the 2016 Tory leadership race that handed the Conservative crown to Mrs May; her resignation might be the catalyst to end her colleague’s time in Downing St.

A No 10 spokesman said: “Andrea Leadsom has served with distinction and great ability as a member of the Government and the Prime Minister is grateful for all of her work. We are disappointed she has chosen to resign and the Prime Minister remains focused on delivering the Brexit people voted for.”

In her letter of resignation the leading Brexiteer said she had considered carefully the timing of her decision, given it came on the eve of the European elections, but explained she had quit ahead of Thursday's Business Statement to MPs because she felt she could not announce a Bill with "new elements that I fundamentally oppose".

She told the PM: "I fully respect the integrity, resolution and determination that you have shown during your time as Prime Minister. No one has wanted you to succeed more than I have…”

But Tom Watson, the deputy Labour leader, criticised Mrs Leadsom's decision to step down on the eve of the European elections, calling it a "slap in the face" for her Tory colleagues.

Ian Blackford for the SNP claimed Mrs May was “barely in office, let alone power” and added: “The Tory Government is falling apart before our very eyes. This chaotic and crumbling government is a far cry from Theresa May’s strong and stable rhetoric.

Scotland deserves better than being held hostage by a Tory Party in open leadership warfare,” he added.

In her letter of resignation, Mrs Leadsom urged the PM to “make the right decisions in the interests of the country, this Government and our party".

This was regarded as a plea for Mrs May to go; an exhortation several ministers and MPs made throughout another bruising day for their party leader.

One senior minister declared: “She has to go now. We are not sitting on Friday and that means another 10 days of this if she doesn’t.”

The backlash to the reworked Withdrawal Agreement Bill[WAB] – which will be published on Friday – led to no fewer than four Cabinet ministers demanding a private meeting with the PM to air their grievances. They included Jeremy Hunt, Sajid Javid and Penny Mordaunt; all regarded as contenders for the leadership.

The fourth was David Mundell who wanted to complain to Mrs May about her pledge to give MPs a vote on a second EU referendum.

A source close to the Scottish Secretary told The Herald: “The Secretary of State is voicing concerns about the way the bill is being presented; it’s sounding as though we are supporting it. This needs to be challenged; the Government does not support a second referendum.”

He added: “The way it’s being presented is being exploited by the Scottish Government and the SNP.”

However, adding tension to an already tense situation, the PM refused to meet any of her colleagues.

Later, after Julian Smith, the Chief Whip, met executive members of the Conservatives’ backbench 1922 Committee, it was announced Mrs May would meet Sir Graham Brady, its Chairman, on Friday to “discuss matters of interest”.

It is widely believed Cabinet ministers have not already gone to Mrs May to demand her resignation for fear of the effect this will have on what the Tories already believe will be disastrous Euro-poll results. But such a demand could come within 48 hours.

One Scottish Tory MP said: “I have always said she should leave with her dignity. That time is now. No later than Friday. Otherwise, it will all break loose on the week of a state visit from our most important ally and of the 75th anniversary of D-day. That would be shameful.”