Development and validation of a ultraperformance liquid chromatography-tandem mass spectrometry method for quantifying free and total dabigatran in human plasma: An application for a bioequivalence study.

Dabigatran etexilate mesylate (DABE), a prodrug, quickly changes into dabigatran (DAB) after its oral administration. Accordingly, detecting DABE in plasma is practically unmanageable. An ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique was developed and validated to compute free DAB in participants. For the first time, the central composite design, a type of response surface methodology, was applied for optimizing variables affecting the cleavage of glucuronide bond. In addition, the pharmacokinetic parameters of generic medication (okanadab) were determined, and the obtained outcomes were compared with those of the branded drug (pradaxa). The sample preparation was done using methanol as a protein precipitant and the separation was achieved using an ACQUITY UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm). The elution was isocratically conducted using 10 mM ammonium formate:methanol (72:28, v/v) as a mobile phase and the flow rate was 0.25 mL/min. Multiple reaction monitoring and positive electrospray ionization were used. The determination was performed within 1 min, and the calibration growth curve was established over a range of 1.19-475 ng/mL using DAB-d3 as a tagged internal standard. Bioequivalence research was validated following the US Food and Drug Administration (US FDA) guidelines for bioanalytical procedures and acceptable outcomes were achieved. The outcomes for okanadab and pradaxa did not differ significantly.

Dexmedetomidine as a part of general anaesthesia for caesarean delivery in patients with pre-eclampsia: A randomised double-blinded trial.

BACKGROUND: During general anaesthesia, endotracheal intubation of patients with pre-eclampsia causes stimulation of the sympathetic nervous system and catecholamine release, which may lead to maternal and neonatal complications. OBJECTIVE: To attenuate both the stress response and the haemodynamic response to tracheal intubation in patients with pre-eclampsia. DESIGN: A randomised, double-blind, controlled study. SETTING: Single University Hospital. PATIENTS: Sixty patients aged 18 to 45 years with pre-eclampsia receiving general anaesthesia for caesarean section. INTERVENTIONS: The patients were randomly allocated to three groups. Groups D1and D2 received an infusion of dexmedetomidine 1 µg kg over the 10 min before induction of general anaesthesia, then 0.4 and 0.6 µg kg h dexmedetomidine, respectively. Group C received equivalent volumes of 0.9% saline. MAIN OUTCOME MEASURES: The primary outcome was the effect of dexmedetomidine on mean arterial blood pressure measured before induction of general anaesthesia at 1 and 5 min after intubation, and then every 5 min until 10 min after extubation. The secondary outcomes were blood glucose and serum cortisol (measured before induction of general anaesthesia, and at 1 and 5 min after intubation), postoperative visual analogue pain scores, time to first request for analgesia, the total consumption of analgesia, Ramsay sedation score, maternal and placental vein blood serum levels of dexmedetomidine and neonatal Apgar score at 1 and 5 min. RESULTS: At all assessment times, the mean arterial pressures were significantly lower in the dexmedetomidine groups than in the control group. Compared with group C, the heart rate was significantly lower in both groups D1 and D2. In group D2, the heart rate was lower than in group D1. Serum glucose and cortisol were significantly higher in the controls than in either group D1 or D2. Group D2 patients were significantly more sedated on arrival in the recovery room followed by D1. Time to first analgesia was significantly longer in groups D2 and D1 than in group C, and the visual analogue pain scores were significantly lower in groups D1 and D2 than in group C at 1, 2, 3 and 5 h. Total morphine consumption was significantly lower in groups D1 and D2 than in the control group. There was no difference in Apgar scores across the three groups despite significantly higher dexmedetomidine concentrations in group D2 (both maternal and placental vein) than in group D1. CONCLUSION: Administration of dexmedetomidine in doses 0.4 and 0.6 µg kg h was associated with haemodynamic and hormonal stability, without causing significant adverse neonatal outcome. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR201706002303170), (www.pactr.org).