OBJECTIVES

In response to the need for a simple and fast way of ensuring that generic drugs especially those that contain rifampicin are bioequivalent with reference drugs, this study validated an ultra-high-performance liquid chromatography (UHPLC) method of quantifying rifampicin in human plasma. The study also validated the method's selectivity, linearity, sensitivity, accuracy, precision, and the absence of a carry-over effect adhering to the Philippine Food and Drug Administration guidelines.

Plasma samples were prepared via protein precipitation using methanol containing ascorbic acid. Three microliters (3 uL) of the prepared samples were then analyzed in a Waters Acquity H-Class UPLC® system coupled to a tunable ultraviolet (TUV) detector with an attached UPLC® BEH C-18 column using a developed and optimized method. Briefly, the column temperature was set to 40°C and the sample temperature was set to 10°C. Elution was done using a linear gradient flow of a water-acetonitrile mixture that started with 45% acetonitrile increasing to 60% acetonitrile at 0.5 minutes and back to 45% acetonitrile at 3 minutes and having a constant flow rate of 0.5 mL/min. Detection was done at 340 nm. Method validation was performed following the ICH guidelines for Bioanalytical Method Validation, the same guidelines referenced by the ASEAN Guideline for Harmonisation of Standards and the Philippine Food and Drug Administration (FDA).

The method had an analysis time of 3 minutes wherein rifampicin eluted at 1.4 minutes while the internal standard, rifapentine (IS) eluted at 1.7 minutes. Since no co-eluting endogenous materials were observed for the rifampicin and the internal standard, the method was confirmed to be selective. Its linearity over the range of 2 ug/mL to 25 ug/mL has been validated where it has a limit of detection (LOD) and limit of quantification (LOQ) values of 0.64 ug/mL and 1.94 ug/mL, respectively. The interday and intraday precision, reported as % coefficient of variance (%CV), and interday and intraday accuracy, reported as %error all within the limits of ±20% for the LLOQ and ±15% for the rest indicating its reliability and reproducibility. Lastly, due to the nature of the injection of the sample into the system, wherein a blank immediately follows the highest concentration standard, the method has been cleared of a carry-over effect.

The study successfully validated a UHPLC method of quantifying rifampicin in human plasma. Due to the sample processing method used and the chromatographic conditions set, the method can prepare and analyze samples in a simple yet fast, sensitive, reliable, and reproducible manner. The method can be applied in bioavailability and bioequivalence studies of rifampicin.

No abstract available.
Therapeutic Equivalency*

No abstract available.
Adult* ; Humans ; Therapeutic Equivalency*

The bioequivalence of two formulations (reference and Vietnamese tested formulation) of racemic chlorpheniramine combined with phenylpropanolamine was assessed in an open-labeled, randomized, crossover two-period study in 12 healthy Vietnamese males aged between 22 and 43 years old, weight between 48kg and 72kg. All 12 subjects received both formulations after an overnight fast and a 7 day wash-out period. Plasma samples were collected up to 168 hours. Plasma concentrations of total chlorpheniramine and individual enantiomers were determined with a validated chiral HPLC method and pharmacokinetic parameters were estimated using a model independent analysis. Bioequivalence was assessed by several different published statistical methods (ANOVA, Confidence Interval, Westlake, and Schuirmann). Results showed that bioequivalence may depend on the statistical and analytical methods used
Chlorpheniramine ; Therapeutic Equivalency

No abstract available.
Chromatography, Liquid* ; Ciprofloxacin* ; Therapeutic Equivalency*

Bioequivalents of two preparations composing of Ranitidine. A randomised crossover controlled single dose study was performed on 18 healthy volumteers (9 males and 5 females) aged from 22 to 40 years old. For each subject of each preparation 1 tablet composing of 150mg of ranitidine was administered orally. Plasma levels of ranitidine were evaluated by HPLC. The dissolution rate of different preparations showed that their properties were similar. Bioequivalent was evalnated statistacally (by diverse methods as ANOVA, confidence interval, West lke and Schurimann). No significant difference in plasma level of these 2 preparations was reforted. No side effect was noted
Ranitidine ; Therapeutic Equivalency ; Pharmaceutical Preparations

A bioequivalence study is usually conducted with the same-day drug administration. However, hospitalization is occasionally separated for logistical, operational, or other reasons. Recently, there was a case of separate hospitalization because of difficulties in subject recruitment. This article suggests a better way of bioequivalence data analysis for the case of separate hospitalization. The key features are (1) considering the hospitalization date as a random effect than a fixed effect and 2) using “PROC MIXED” instead of “PROC GLM” to include incomplete subject data.
Hospitalization* ; Statistics as Topic* ; Therapeutic Equivalency*

The structural complexity of crossover studies for bioequivalence test confuses analysts and leaves them a hard choice among various programs. Our study reviews PROC GLM and PROC MIXED in SAS and compares widely used SAS codes for crossover studies. PROC MIXED based on REML is more recommended since it provides best linear unbiased estimator of the random between-subject effects and its variance. Our study also considers the covariance structure within subject over period which most PK/PD studies and crossover studies ignore. The QT interval data after the administration of moxifloxacin for a fixed time point are analyzed for the comparison of representative SAS codes for crossover studies.
Cross-Over Studies* ; Therapeutic Equivalency

OBJECTIVETo explore the way for testing of multivariate in therapeutical equivalence.

METHODSBy improved Hotelling T(2) test, the mean vector of two groups was tested. The information of each variable could then be obtained by deducting the their correlations. "Clinical Equivalence of Drug A and Drug B for Postmenopausal Bone Looseness" was used in this research. The primary measure of efficacy was regarded as the improvement rate of four variables with predefined limit of equivalence (2%) with the results of univariate test and multivariate test compared.

RESULTSUnder P > alpha, all the variables were nonequivalent. Under P

CONCLUSIONWith the combination of the filtration of nonequivalent variables and the improved Hotelling T(2) test, the test of multivariate could be done. The method is reasonable and practical.

Bioequivalence is defined as the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar experimental conditions in either a single dose or multiple doses in an appropriately designed study. If a drug is to be bioequivalent to the reference drug, the confidence interval for both pharmacokinetic parameters, AUC(area under the plasma concentration-time curve) and Cmax(maximal plasma concentration), must be entirely within the 80% to 125% of those of the reference drug. Underlying the concept of bioequivalence is the thesis that, if a drug product contains a drug substance that is chemically identical and is delivered to the site of action at the same rate and extent as another drug product, then it is equivalent and can be substituted for that drug product. The primary concern from the regulatory point of view is the protection of the patient against approval of products that are not bioequivalent. In this paper the general concept and the practical significance of the bioequivalence is described. The recently revised Korean guideline for bioequivalence test is also discussed.
Drug Substitution ; Humans ; Molar ; Plasma ; Therapeutic Equivalency*