Liquid chromatography-tandem mass spectrometry quantification of levosulpiride in human plasma and its application to bioequivalence study.

An improved method for determining levels of levosulpiride in human plasma using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated. The protein precipitation method was used for plasma sample preparation. Levosulpiride and an internal standard (IS) were isocratically separated on a UPLC BEH C(18) column with a mobile phase of ammonium formate buffer (1mM, adjusted to pH 3 with formic acid) and acetonitrile (60:40, v/v). MS/MS detection was performed by monitoring the parent-->daughter pair of levosulpiride and the IS at m/z 342-->112 and 329-->256, respectively. The method was linear from 2.5 to 200ng/mL and exhibited acceptable precision and percent recovery. The method was successfully demonstrated in pharmacokinetic and bioequivalence studies of two levosulpiride oral formulations administered to healthy volunteers. When compared to the previous LC-MS methods, the proposed method is faster, well-validated, and uses lesser plasma volume and a similar sensitivity. The use of UPLC allowed rapid and sensitive quantification of levosulpiride, making this method suitable for high-throughput clinical applications.

Rapid determination of finasteride in human plasma by UPLC-MS/MS and its application to clinical pharmacokinetic study.

A rapid, specific, and sensitive method utilizing reversed-phase ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed and validated to determine finasteride levels in human plasma. The plasma samples were prepared by liquid-liquid extraction with ethyl acetate, evaporation, and reconstitution. MS/MS analyses were performed on a triple-quadrupole tandem mass spectrometer by monitoring protonated parent-->daughter ion pairs at m/z 373-->305 for finasteride and m/z 237-->194 for carbamazepine (internal standard, IS). The method was validated with respect to linearity, recovery, specificity, accuracy, precision, and stability. The method exhibited a linear response from 0.1 to 30 ng/mL (r(2)>0.998). The limit of quantitation for finasteride in plasma was 0.1 ng/mL. The relative standard deviation (RSD) of intra- and inter-day measurements was less than 15% and the method was accurate within -6.0% to 2.31% at all quality-control levels. The mean extraction recovery was higher than 83% for finasteride and 84% for the IS. Plasma samples containing finasteride were stable under the three sets of conditions tested and the processed samples were stable up to 29 h in an autosampler at 5 degrees C. Detection and quantitation of both analytes within 3 min make this method suitable for high-throughput analyses. The method was successfully applied to a pharmacokinetic study of finasteride in healthy volunteers following oral administration.

Distraction osteogenesis of the cranial vault for the treatment of craniofacial synostosis.

From January 2000 to December 2001, six patients with craniosynostosis were treated. Involved sutures were coronal sutures in three patients, coronal and metopic sutures in one patient, multiple sutures (brachycephaly and oxycephaly) in one patient, and multiple sutures with a cloverleaf skull deformity in one patient. The age distribution of the patients was 4 months to 3 years. Four were male, and two were female. A frontal craniotomy was performed in four patients with brachycephaly. In one patient with brachycephaly, the osteotomies were made across the nasofrontal junction, across the roof of the orbit, and along the lateral orbital wall. In one patient with a cloverleaf skull deformity, a frontal bone osteotomy was first performed 1 cm above the roof of the orbit. A supraorbital frontal bar was then made across the nasofrontal junction, across the roof of the orbit, and down to the lateral orbital wall. The frontal bone flap was repositioned to the supraorbital bar using absorbable miniplates and screws. Distraction was started 3 to 7 days after the operation at a distraction rate of 1 mm/d. The real duration of the first operation was 90 to 120 minutes, and the second operation to remove the device took 40 to 50 minutes to perform. The distracted length was 15 to 25 mm. The consolidation period was 3 to 5 weeks. The follow-up period was 6 months to 1 year. Postoperative three-dimensional computed tomography demonstrated reossification at the bone flap and advancement of the fronto-orbital area. After surgery, the cranial volume increased 22.7% on average compared with before surgery. The mean ratio of the anteroposterior length to the transverse length of the cranial vault was changed from 0.96 before surgery to 1.04 after surgery. In conclusion, the advantages of distraction osteogenesis of the cranial vault are that it offers a less invasive technique, a shorter operation time, easy care, and postoperative safety as a result of minimal dissection of the dura. Disadvantages are the limited possibility of initial reshaping and the necessity of one more operation for device removal.