Development of a validated high‐throughput LC‐ESI‐MS method for determination of sirolimus on dried blood spots

Abstract

A high-throughput liquid chromatography-electrospray ionization mass spectrometric (LC-ESI-MS) method for screening of sirolimus on dried blood spots (DBS) was developed and validated. It involves solvent extraction of a punch of DBS followed by reversed-phase LC on a relatively new monolithic column consisting of a silica rod with bimodal pore structure and detection by ESI-MS. The run time was less than 3 min with a very low backpressure at a flow rate of 0.5 mL/min. The method can analyze more than 100 samples in an 8 h working day, including sample preparation. The assay was linear from 1 to 100 ng/mL. The mean recovery was 92.42%. The mean inter-day and intra-day precisions were 1.23 and 1.41%, respectively. The developed method is simple, rapid and useful for clinical applications.

Applications of monolithic columns in liquid chromatography‐based clinical chemistry assays

“…Busulfan has been quantified in both saliva and plasma with an LOQ of 0.04 mmol/L (10 ng/ mL), a linear range of 0.04-10.15 mmol/L (10-2500 ng/mL), and a CV of o4% [28]. Finally, a sirolimus method for dried blood spots has an LOQ of 1.1 nmol/L (1.0 ng/mL), linear range up to 0.11 mmol/L (100 ng/mL), and a CV of r3.2% [29]. In this report, the multi-criteria optimization methodology was again used to develop the chromatographic method.…”

“…(100 Â 4.6 mm) [28] Mycophenolic acid, mycophenolic acid glucuronide [24][25][26] Cyclosporin A [27] Busulfan [28] Sirolimus [29] Blood pressure drugs HPLC-fluorescence [30][31][32]34], HPLC-UV [33], HPLC-MS/MS [35] Plasma [30][31][32][33]35], urine [30,34] Chromolith Performance RP-18e (100…”

“…(100 Â 4.6 mm) [23] Bupropion, hydroxybupropion, threohydrobupropion, erythrohydrobupropion [21] Escitalopram [22] Quetiapine [23] Immunosuppresants HPLC-UV [24][25][26], HPLC-MS/MS [28], [24][25][26][27][28], urine [26], saliva [28], dried blood spot [29] Chromolith Performance RP-18e (100…”

Antineoplastic drugs and their analysis: a state of the art review

“…617 Blood sample analysis on blotting paper was particularly useful in the case of mTOR inhibitors by facilitating the collection and processing of the sample prior to LC-MS analysis. [618][619][620][621][622] Under such conditions, concentrations in the order of ng mL −1 were detected. It can be noted that MS detection of mTOR inhibitors was mainly performed via adducts formation including sodium adducts 601,602 or ammonia adducts 623,624,625 because of the neutral character of these molecules.…”

Molecularly imprinted polymer for selective extraction of 3‐methylflavone‐8‐carboxylic acid from human urine followed by its determination using zwitterionic hydrophilic interaction liquid chromatography

“…Table 4 summarizes the intra-and inter-run performance data. All the values obtained were well within internationally recognized acceptance criteria for assay validations and were within the pre-defined limits (not exceeding 15% of the coefficient of variation (CV)) [26,27]. The lower limit of quantification for the analysis of MIP extracts was 1.2 mg/mL of urine.…”