Elimination of sufentanil following epidural administration was very slow, with MRT = 28.25 [18.36-44.75] h and t1/2 MRT  = 19.57 [12.72-31.01] h. In infants, during a long-term infusion of sufentanil with ropivacaine, the opioid concentration in plasma increases during the postoperative infusion itself, then increases even further after discontinuation of the infusion, in some cases reaching the values consistent with a potential risk of respiratory depression. Meticulous monitoring of the infants' vital signs is therefore mandatory not only during the infusion, but also for several hours after its discontinuation.

The relatively simple liquid-liquid extraction LC-MS/MS method using a UPLC column for measurement of digoxin concentrations both in medium and human plasma is described. Digitoxin was used as internal standard. The developed method possesses satisfactory accuracy, precision, and repeatability, and is economical and not time-consuming. It is the first method for precise measurement of digoxin concentrations in human plasma using combined HPLC equipment and UPLC column with a low limit of quantitation equal to 0.1 ng ml -1 as verified in more than 1500 samples analyzed in a GCP GLP bioequivalence study. The developed method was successfully used in digoxin bioequivalence studies in which 26 volunteers were enrolled.

With this dosing regimen, fentanyl concentration in plasma was within the range of analgesic concentrations, and did not exceed 1.0 ng·ml(-1) . After discontinuation of epidural infusion, pharmacokinetics of fentanyl was complicated by a slight increase in plasma concentration during the elimination phase. Both elimination half-life of fentanyl (t1/2, MRT ) and mean residence time (MRT) were much longer than those observed after single IV bolus dose, and longer in Group I than in Group II (t1/2 MRT 15.9 [3.6-31.5] h vs 8.0 [7.1-13.3] h, P < 0.05, MRTstop-last 22.9 [5.1-45.5] h vs 11.5 [10.2-19.1] h, P < 0.05). Therefore, monitoring of vital signs seems warranted for several hours after the termination of the epidural infusion because risk of respiratory depression may persist, especially in the younger age group.

The aim of this study was to verify the values of maximal observed concentration (C max,obs) and the time, at which maximum concentration is observed (t max,obs) using the analysis of the absorption rate constant (k ab). It focused on the changes in concentration over time (C-T) for drugs, for which several peaks of concentration occur. In addition, the attempt was made to use Fibonacci sequence to facilitate the visual analysis of the dynamics in changes of concentration on C-T graphs. The analyses were conducted with the use of three hypothetical data groups (groups I, II and III), which had distinct C-T profiles, and with the in vivo data form healthy subjects (n = 10) taking part in a bioequivalence study, who was given a single oral dose of topiramate (100 mg). The comparison of hypothetical and real in vivo data demonstrated that for the C-T curves, in which there are several peaks of concentration C max,obs and t max,obs values can easily be miscalculated when the increase in concentration is not properly related to the appropriate absorption phase (63.2, 87.50, 96.88 %). It was also demonstrated that the data transformation with the use of Fibonacci sequence exposes slight differences in the observed concentration values in a semi-logarithmic scale. The results of this study show that in case of C-T curves with several peaks of concentration, the verification of C max and t max data obtained taking into account different absorption phases enables more precise evaluation of these parameters.

A HPLC/mass spectrometry method for the estimation of itraconazole (CAS 84625-61-6, ITR) and its active metabolite hydroxyitraconazole (CAS 112559-91-8, HOX) in human plasma was developed. Terconazole (CAS 67915-31-5) was used as an internal standard. The analytical method was fully validated according to FDA and EMEA requirements. The accuracy and precision of the developed method was satisfactory and stability studies showed an acceptable variation (below 15%) of ITR and HOX concentrations when the samples were stored frozen at -75 degrees C for 95 days. The developed method was successfully used for a comparative 2 x 2 period, crossover bioequivalence study of two preparations of ITR (Itrakonazol Genexo 100 mg as the test drug) performed on 36 healthy volunteers.