“…In the majority of the in-tube SPME applications, acetonitrile has been employed to facilitate protein precipitation in plasma samples [33][34][35]80,83,86,103,125,[134][135][136][137][138]. Alternatively pure methanol [121,140,141], 1% acetic acid in acetonitrile [79], or mixtures of acetonitrile/methanol 90/10 v/v have been also utilized for this purpose [139]. Moreover, some approaches followed the direct dilution of plasma samples in 0.1 % v/v aqueous formic acid solution [37,46], 1 % v/v aqueous acetic acid solution [40,78,93,144], phosphate buffer [60,66,88,143], or a mixture of phosphate buffer/acetonitrile 90/10 v/v [62] and phosphate buffer/methanol 95/5 v/v [85].…”