Clinical validation of dried blood spot sampling in therapeutic drug monitoring of ciclosporin A in allogeneic stem cell transplant recipients: direct comparison between capillary and venous sampling.

BACKGROUND: The immunosuppressive drug ciclosporin A has a narrow therapeutic window and a large inter- and intraindividual pharmacokinetic variability. Therapeutic drug monitoring of ciclosporin is usually performed in ethylenediaminetetraacetic acid blood, obtained by venous sampling. Dried blood spot sampling (DBS) could be a useful alternative sampling method, which also easily allows multiple sampling, for example, for obtaining area under the curve. With DBS, capillary blood is obtained from a finger prick with an automatic lancet by the patients themselves, and the drop of blood is applied to sampling paper. This may limit the number and duration of hospital visits for these patients. METHODS: We describe a validation study in which venous and finger prick blood samples were collected at the same time. Venous sampling was performed by venipuncture, and the ethylenediaminetetraacetic acid blood samples were collected and stored at 4°C until analysis. Finger prick blood samples were collected using an automatic lancing device. The volume of the blood drops of patients was approximately 30 µL, and blood spots of about 10-mm diameter were produced. Paper disks with a diameter of 8 mm were punched out with an electromagnetic-driven hole puncher. DBS was compared with the routine assay in venous blood. The study population consisted of adult patients (18 years or older) who were treated with ciclosporin A and routinely monitored for adequate blood concentrations. RESULTS: Thirty-eight duplicate dried blood spots and venous samples were studied. Using weighted Deming regression, the slope was 1.01 with a standard error of 0.03 associated with an intercept of -9.0 (standard error = 5.9). These results indicate that there is no significant difference between the 2 sampling methods. For the medical decision level of 300 mcg/L, the bias was -4.7 mcg/L with a 95% confidence interval of -19.2 to 9.8 mcg/L. The Altman-Bland plot showed no difference between the 2 sampling methods. CONCLUSIONS: Our results demonstrate that DBS is a valid alternative for conventional venous sampling in allogeneic stem cell transplant recipients.

Rapid quantification of gabapentin, pregabalin, and vigabatrin in human serum by ultraperformance liquid chromatography with mass-spectrometric detection.

BACKGROUND: Gabapentin (GBP), pregabalin (PRG), and vigabatrin (VIG) are used for the prevention and treatment of epileptic seizures. The developed method was applied to samples from subjects participating in a pharmacokinetic study of GBP. METHODS: Sample pretreatment consisted of adding 20 µL of trichloroacetic acid (30%; vol/vol) and 200 µL of GBP-d4 in acetonitrile as an internal standard to 20 µL of serum. Chromatographic separation was performed on an Acquity separation module using a Kinetex RP18 column. The aqueous and organic mobile phases were 2 mM ammonium acetate supplemented with 0.1% formic acid in water and acetonitrile, respectively. The detection by a tandem quadrupole mass spectrometer, operating in the positive mode using multiple reaction monitoring, was completed within 2 minutes. RESULTS: The method was linear over the range of 0.03-25 mg/L for GBP, 0.03-25 mg/L for PRG, and 0.06-50 mg/L for VIG. The between- and within-run accuracies ranged from 90% to 107%. The between- and within-run imprecisions of the method were <10%. Stability data show no significant decrease of the analytes. A relative matrix effect of -1%, 0.2%, and -5% was determined for GBP, PRG, and VIG, respectively. CONCLUSIONS: A simple and sensitive ultraperformance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of GBP, PRG, and VIG in human serum. The reported method provided the necessary linearity, precision, and accuracy to allow the determination of GBP, PRG, and VIG for therapeutic drug monitoring and clinical research purposes.