A method for determining hydrolase activity in a sample, comprising the following steps: a) incubating the sample or an aliquot thereof and a buffered solution to form an incubated sample, wherein the buffered solution comprises a buffer substance, an artificial hydrolase substrate, a salt and bovine serum albumin, wherein the sample comprises a therapeutic polypeptide, wherein the artificial hydrolase substrate comprises an ester bond covalently linking a carboxylic acid residue, which is conjugated to a first label, and an alcohol residue, which is conjugated to a nucleic acid tag and a second label, which is different from the first label, wherein the ester bond in the artificial hydrolase substrate is cleaved into a free alcohol residue and a free carboxylic acid residue if hydrolase activity and/or a hydrolase is present in the sample, b) removing the free carboxylic acid residue and artificial hydrolase substrate from the incubated sample to obtain a depleted sample, wherein the removing is by contacting the incubated sample with a first solid phase, which specifically binds to the first label, and separating the free carboxylic acid- and artificial hydrolase substrate-depleted incubation mixture from the first solid phase thereafter, c) determining hydrolase activity and/or the presence of a hydrolase in the sample by determining the second label in the depleted sample, wherein the determining is by capturing the free alcohol residue on a second solid phase via the nucleic acid tag followed by detecting the solid-phase captured free alcohol residue with an antibody specifically binding to the second label, which antibody is conjugated to one or more detectable labels. a) incubating the sample or an aliquot thereof and a buffered solution to form an incubated sample, wherein the buffered solution comprises a buffer substance, an artificial hydrolase substrate, a salt and bovine serum albumin, wherein the sample comprises a therapeutic polypeptide, wherein the artificial hydrolase substrate comprises an ester bond covalently linking a carboxylic acid residue, which is conjugated to a first label, and an alcohol residue, which is conjugated to a nucleic acid tag and a second label, which is different from the first label, wherein the ester bond in the artificial hydrolase substrate is cleaved into a free alcohol residue and a free carboxylic acid residue if hydrolase activity and/or a hydrolase is present in the sample, wherein the buffered solution comprises a buffer substance, an artificial hydrolase substrate, a salt and bovine serum albumin, wherein the sample comprises a therapeutic polypeptide, wherein the artificial hydrolase substrate comprises an ester bond covalently linking a carboxylic acid residue, which is conjugated to a first label, and an alcohol residue, which is conjugated to a nucleic acid tag and a second label, which is different from the first label, wherein the ester bond in the artificial hydrolase substrate is cleaved into a free alcohol residue and a free carboxylic acid residue if hydrolase activity and/or a hydrolase is present in the sample, b) removing the free carboxylic acid residue and artificial hydrolase substrate from the incubated sample to obtain a depleted sample, wherein the removing is by contacting the incubated sample with a first solid phase, which specifically binds to the first label, and separating the free carboxylic acid- and artificial hydrolase substrate-depleted incubation mixture from the first solid phase thereafter, c) determining hydrolase activity and/or the presence of a hydrolase in the sample by determining the second label in the depleted sample, wherein the determining is by capturing the free alcohol residue on a second solid phase via the nucleic acid tag followed by detecting the solid-phase captured free alcohol residue with an antibody specifically binding to the second label, which antibody is conjugated to one or more detectable labels.