Graham Lawson, Hussain Mulla and Sangeeta Tanna
The use of blood spot collection cards was investigated as a means of obtaining small volume samples for the analysis of therapeutic drugs for the purpose of neonatal pharmacokinetic studies. We describe the development of two micro-analytical methods for the determination of captopril extracted from dried blood spots (DBS). Firstly a liquid chromatography ion-trap mass spectrometry method with selected ion monitoring (LC-MS(SIM)) of target ion at m/z 218.0 was developed to determine captopril levels in 8mm discs punched from each DBS. This was compared in terms of specificity and sensitivity to a simple accurate mass liquid chromatography high resolution TOF mass spectrometry (LC-HRMS) method in which MS detection was carried out in electrospray positive ion mode for target ions at m/z 218.0845 for captopril and 377.2084 for the IS. Dithiothreitol was used both to pre-treat the sampling cards and as part of the extraction medium in order to stabilise the DBS extracted captopril. Drug extraction efficiency from spiked blood spots was demonstrated to be 90 ± 10% and the drug was stable in DBS for at least 12 weeks. Validation of both micro-analytical methods showed good precision and accuracy and the LC-HRMS method was linear within the tested calibration range 10-400 ng/ml for captopril and had improved sensitivity and specificity compared to the LC-MS(SIM) method. This method was applied to blood spots on sampling card from a neonate patient previously administered 1 mg/kg captopril orally. The amount of captopril in the DBS was 88 ng/ml. Requiring only a micro volume (30 μl) blood sample for analysis, the developed DBS based micro-analytical method has the potential to facilitate pharmacokinetic studies of captopril in children.
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