Tumors of the foot and ankle: a single-institution experience.

Tumors of the foot and ankle are rare, and the particular clinicopathologic features, therapeutic approach, and outcomes in this setting are not well established. From January 2000 to December 2010, 72 patients with primary musculoskeletal tumors of the foot and ankle, both benign and malignant, were treated at a single institution. Of the 72 patients, 56% were female. The median age was 52 years. Of the 72 tumors, 62 (86.11%) were located in the foot and 10 were located in the ankle; 63 (87.5%) were soft tissue tumors and 9 (12.5%) were bone tumors. Overall, 56 (78%) were benign tumors and 16 (22%) were malignant tumors. The most frequent soft tissue and bone diagnosis was giant cell tumor. The median follow-up period was 49 months. The vast majority of the tumors were located in the foot. Benign tumors were dominant, outnumbering malignant tumors by more than 3 to 1. The diversity of the histologic benign types was evident, with giant cell tumor, angiomyoma, and lipoma the most frequent. Regarding the malignant tumors, a clear male predominance was present, the median age was 45 years, and the most frequent tumor was synoviosarcoma. The 9-year overall and disease-free survival rate was 65% and 40%, respectively.

Development and validation of a rapid and sensitive LC-ESI-MS/MS method for ondansetron quantification in human plasma and its application in comparative bioavailability study.

The validation of a high throughput and specific method using a high-performance liquid chromatography coupled to electrospray (ES+) ionization tandem triple quadrupole mass spectrometric (LC-ESI-MS/MS) method for ondansetron quantification in human plasma is described. Human plasma samples were extracted by liquid-liquid extraction (LLE) using methyl tert-butyl ether and analyzed by LC-ESI-MS/MS. The limit of quantification was 0.2 ng/mL and the method was linear in the range 0.2-60 ng/mL. The intra-assay precisions ranged from 1.6 to 7.7%, while inter-assay precisions ranged from 2.1 to 5.1%. The intra-assay accuracies ranged from 97.5 to 108.2%, and the inter-assay accuracies ranged from 97.3 to 107.0%. The analytical method was applied to evaluate the relative bioavailability of two pharmaceutical formulations containing 8 mg of ondansetron each in 25 healthy volunteers using a randomized, two-period crossover design. The geometric mean and respective 90% confidence interval (CI) of ondansetron test/reference percent ratios were 90.15% (81.74-99.44%) for C(max) and 93.11% (83.01-104.43%) for AUC(0-t). Based on the 90% confidence interval of the individual ratios (test formulation/reference formulation) for C(max) and AUC(0-inf), it was concluded that the test formulation is bioequivalent to the reference one with respect to the rate and extent of absorption of ondansetron.

Simultaneous determination of losartan and hydrochlorothiazide in human plasma by LC/MS/MS with electrospray ionization and its application to pharmacokinetics.

A method based on a simple liquid-liquid extraction (LLE) followed by high-performance liquid chromatography with negative ion electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) detection was developed for the simultaneous determination of losartan (LOS) and hydrochlorothiazide (HCTZ) in human plasma, using valsartan (VAL) and chlorthalidone (CHTD) as an internal standard, respectively. The acquisition was performed in multiple reactions monitoring (MRM) and the limit of quantification was 4 ng/mL for both LOS and HCTZ. The method was linear in the studied range (4-800 ng/mL for LOS and 4-500 ng/mL for HCTZ). The intra-assay precisions ranged from 2.6-11.9% for LOS and 1.4-8.2% for HCTZ, while the inter-assay precisions ranged from 1.0-8.0% for LOS and 2.5-7.7% for HCTZ. The intra-assay accuracies ranged from 91.3 to 107.6% for LOS and 91.5 to 105.8% for HCTZ, while the inter-assay accuracies ranged from 99.9 to 106.4% for LOS and 97.4 to 101.4% for HCTZ. The analytical method was applied to a bioequivalence study, in which 28 healthy adult volunteers (14 men) received single oral doses (100 mg LOS + 25 mg HCTZ) of reference and test formulations, in an open, two-period, balanced randomized, crossover protocol. Based on the 90% confidence interval of the individual ratios for Cmax and AUC0-inf, it was concluded that the test formulation is bioequivalent to the reference Hyzaar formulation with respect to the rate and extent of absorption of both LOS and HCTZ.

Determination of bromazepam in human plasma by high-performance liquid chromatography with electrospray ionization tandem mass spectrometric detection: application to a bioequivalence study.

A simple method using a one-step liquid-liquid extraction (LLE) followed by high-performance liquid chromatography (HPLC) with positive ion electrospray ionization tandem mass spectrometric (ESI-MS/MS) detection was developed for the determination of bromazepam in human plasma, using lorazepam as internal standard. The acquisition was performed in the multiple reaction monitoring mode, monitoring the transitions: m/z 316 > 182 for bromazepam and m/z 321 > 275 for lorazepam. The method was linear over the studied range (1-100 ng ml(-1)), with r(2) > 0.98, and the run time was 2.5 min. The intra- and inter-assay precisions were 2.7-14.6 and 4.1-17.3%, respectively and the intra- and inter-assay accuracies were 87-111 and 75.8-109.5%, respectively. The mean recovery was 73.7%, ranging from 64.5 to 79.7%. The limit of quantification was 1 ng ml(-1). At this concentration the mean intra- and inter-assay precisions were 14.6 and 7.1%, respectively, and the mean intra- and inter-assay accuracies were 102.5 and 104%, respectively. Bromazepam stability was evaluated and the results showed that the drug is stable in standard solution and in plasma samples under typical storage and processing conditions. The method was applied to a bioequivalence study in which 27 healthy adult volunteers (14 men) received single oral doses (6 mg) of reference and test bromazepam formulations, in an open, two-period, randomized, crossover protocol. The 90% confidence interval of the individual ratios (test formulation/reference formulation) for C(max) (peak plasma concentration), AUC(0-96) and AUC(0-inf) (area under the plasma concentration versus time curve from time zero to 96 h and to infinity, respectively) were within the range 80-125%, which supports the conclusion that the test formulation is bioequivalent to the reference formulation regarding the rate and extent of bromazepam absorption.

Combined chromatographic methodology for antidoping control in horse urine

A combination of chromatographic techniques is described for the screening of drugs in horse urine for antidoping control purposes. The procedure consists of liquid-liquid base extraction with analysis by HPTLC and GC-NPD and liquid-liquid acidic extraction followed by HPTLC and HPLC. The results of 86 drugs analyzed by these procedures, as well as limits of detection of the drugs in each technique are presented, The use of ELISA tests are recommended for the screening of drugs which would not be detected by the chromatographic proposed procedure. The results show that the proposed combination of techniques enables an efficient antidoping control of racing horses.