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ABSTRACT: Nitazoxanide (NTZ) is used for the treatment of gastrointestinal tract colonization by anaerobic bacteria, viruses and other pathogens that represent a major cause of morbidity in Latin America. The aim of the present work was to develop and validate a UPLC-MS/MS method for the selective quantification of tizoxanide (TZN, the major metabolite of NTZ) in human plasma using niclosamide as internal standard; and examine its pharmacokinetic application in healthy volunteers. Nine male subjects received a single oral dose of a NTZ 500-mg tablet under fasting conditions.
The method was linear between 0.1 and 10 µg/ml and capable of separating signals from free-TZN and those delivered by in-source collision-induced dissociation of TZN-glucuronide, quantifying it with accuracy and precision. Mean maximum plasma concentration was 6.79 µg/ml and was reached at 2.4 h post-dose.
The method was validated, fulfilling regulatory guidelines. Results suggest low pharmacokinetic variability in the assayed population.
Bioanalysis 05/2012; 4(8):909-17. · 3.22 Impact Factor
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ABSTRACT: Sildenafil citrate (SIL) was the first oral drug registered in Mexico for the treatment of erectile dysfunction. However, succinct pharmacokinetic data are available in the Mexican population.
The goals of the present work were: (1) to design a specific method to quantify SIL plasma levels by using UPLC-MS/MS; (2) to compare oral SIL bioavailability in Mexican men with pharmacokinetic data in other populations; (3) to fulfill local regulatory requests; and (4) to describe the relative tolerability of a new 50-mg chewable tablet.
This was a randomized, single-dose, 3-period, 6-sequence crossover study in healthy male volunteers. In each period, subjects received single oral doses of 100 mg of sildenafil (1 commercial [reference(⁎)], 1 generic [test 1(†)], or 2 chewable generic tablets [test 2(‡)]), with a 4-day washout period between each dose. Serial blood samples were collected for up to 24 hours. SIL was measured in heparinized plasma by using a validated UPLC-MS/MS method. Pharmacokinetic parameters included C(max), T(max), AUC(0-24), and AUC(0-∞). Bioequivalence was established if 90% CIs for mean test:reference ratios of log-transformed C(max) and AUC fell within the range of 0.80 to 1.25. Tolerability was assessed on the basis of a clinical interview with the subject and monitoring of vital signs.
Demographic data showed a homogeneous population. Validation of analytical method proved to be linear within the range of 1 to 1000 ng/mL, with selectivity, accuracy, and precision. 90% CIs for test 1:reference ratios were 86.52 to 113.56, 94.75 to 108.84, and 94.97 to 108.82 for the logarithm parameters C(max), AUC(0-24), and AUC(0-∞), respectively. The 90% CIs for the test 2:reference ratios were 82.14 to 107.24, 98.26 to 112.56, and 99.19 to 113.34 for C(max), AUC(0-24), and AUC(0-∞). Regarding relative tolerability, slight cephalea was the most common adverse effect.
The developed analytical method was validated in compliance with local requirements and was useful for sildenafil measurement. This single-dose study under fasting conditions suggests that both test products met the Mexican regulatory criteria for assuming bioequivalence in these healthy, male Mexican volunteers. The clinical data suggest that the chewable tablets were well tolerated by volunteers.
Clinical Therapeutics 03/2012; 34(3):689-98. · 2.32 Impact Factor
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ABSTRACT: Background: A growing number of boron-containing compounds exhibit many important biological activities; of particular interest are the α-amino acid borinic derivatives with activity in the CNS. A validated, sensitive and specific UPLC-MS/MS technique for quantification of the diphenylboroxazolidones of glycine (DBPX-gly), L-aspartate (DPBX-L-asp) and L-glutamate (DPBX-L-glu) in dried blood spots (DBSs) is presented. Results: The most intense signal corresponds to compounds with (11)B. The extraction procedure was liquid elution of 3.2-mm punched DBSs with acetonitrile:aqueous formic acid 0.1% (80:20 v/v). Assays proved to be linear, falling accurately and precisely within the range of 0.3-50 µg/ml for DPBX-L-asp and DPBX-L-glu and 0.1-5 µg/ml for DBPX-gly. Chromatograms exhibit clean 2.0-min running time peaks and S/N ratios for the LLOQ were approximately 15:1. The technique was used to evaluate the pharmacokinetics of the molecules and to correlate these with timecourse toxic effects. Conclusion: DBSs represent an advantage for the collection of small volumes of samples, and also in terms of processing and storage. UPLC-MS/MS allow us not only to identify the isotopic pattern of boron in DBPX, but also to quantify them with accuracy and specificity. Pharmacokinetics of these molecules exhibit a high apparent volume of distribution; it suggests a preference of DPBX-amino acids for fatty tissues such as the CNS.
Bioanalysis 02/2011; 3(4):439-48. · 3.22 Impact Factor
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ABSTRACT: Claw toe deformity sometimes leads to dorsiflexion of the metatarsophalangeal joint (MPJ) and plantar flexion of the proximal (PIPJ) and distal interphalangeal (DIPJ) joints. Flexor digitorum longus tendon transfer (FDL) is currently the gold standard for the correction of this problem. Transfer of the flexor digitorum brevis (FDB) has been recently proposed as an alternative method to treat such deformity. The aim of this work is to compare the biomechanical outcome of these two methods by means of finite-element simulation. The results show that the reduction in the dorsal displacement of the proximal phalanx (PP) for the second and third toes were very similar (about 4.3 mm for each intervention), both achieving a significant reduction in MPJ dorsiflexion when compared to no intervention (displacements are reduced by approximately 51%). In the fourth and fifth toes, only a small correction in the deformity was achieved with both the techniques (10% and 7%, respectively). FDB and FDL tendon transfer reduced the stress level when compared with the non-operated pathologic foot (the reduction of stresses for the second and third PP ranged between 20% and 40%). FDB transfer resulted in a more uniform distribution of stress along the entire toe, although differences were small in all cases. These results confirm that both the tendon-transfer techniques are effective in the treatment of claw toe deformity. Therefore, the choice of technique is at the discretion of the surgeon.
Journal of biomechanics 06/2009; 42(11):1697-704. · 2.66 Impact Factor
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ABSTRACT: The aim was to develop a rapid, specific, sensitive and accurate chromatographic technique coupled with mass spectrometry for the measurement of tacrolimus (CAS 104987-11-3) in microsamples of whole blood, and its application on a pharmacokinetic pilot trial.
A fast gradient was designed in an ultra-performance liquid chromatography, and coupled with a mass spectrometer for the quantification of tacrolimus in 100 microl samples of EDTA whole blood. Multiple reaction monitoring was used for the measurement of tacrolimus (m/z(+1) 821.49-->4768.35 Th) and sirolimus as internal standard (m/z(+1) 931.69-->864.39 Th). The method was validated according to Mexican regulatory guidelines. Twenty-four young healthy male volunteers with similar hematocrit values participated in the pharmacokinetic trial; an oral single dose of one 5 mg tacrolimus capsule was administered and kinetic profiles were described since 0 h until 24 h post-dose.
Method showed to be accurate, precise and linear over the range from 1 to 80 ng/ml, having an absolute recovery of 94%. Molecule was stable for two months at -70 degrees C, and heparin interfered with its quantification. Total run-time is around 1.5 min. Mean maximum blood concentration was 32.63 +/- 1.74 ng/ml, and was reached at 1 h post-dose; elimination half-life was 14.18 +/- 5.71 h.
Method developed is not time-consuming, inexpensive, and sensitive enough for its application during pharmacokinetic trials, and can be suitable for therapeutic drug monitoring in transplanted patients. Pharmacokinetic data obtained in Mexican population are quite similar to previously reported in international literature.
Arzneimittel-Forschung 02/2007; 57(10):659-64. · 0.72 Impact Factor
