Rapid quantification of levosulpiride in human plasma using RP-HPLC-MS/MS for pharmacokinetic and bioequivalence study.

A rapid and validated method for analysis of levosulpiride in human plasma using liquid chromatography coupled to tandem mass spectrometry was developed. Levosulpiride and tiapride (IS, internal standard) were extracted from alkalized plasma samples with ethylacetate and separation by RP-HPLC. Detection was performed by positive ion electrospray ionization in multiple-reaction monitoring mode, monitoring the transitions m/z 342.1 --> m/z 112.2 and m/z 329.1 --> m/z 213.2, for quantification of levosulpiride and IS, respectively. The standard calibration curves showed good linearity within the range of 2-200 ng/mL (r(2) > or = 0.9990). The lower limit of quantitation was 2 ng/mL. The retention times of levosulpiride (0.63 min) and IS (0.66 min) presented a significant time saving benefit of the proposed method. No significant metabolic compounds were found to interfere with the analysis. This method offered good precision and accuracy and was successfully applied for the pharmacokinetic and bioequivalence study of a 25 mg of levosulpiride tablet in 24 healthy Korean volunteers.

Quantification of isradipine in human plasma using LC-MS/MS for pharmacokinetic and bioequivalence study.

A highly sensitive and rapid method for the analysis of isradipine in human plasma using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was developed. The procedure involves a simple liquid-liquid extraction of isradipine and amlodipine (IS, internal standard) with methyl-t-butyl ether after alkaline treatment and separation by RP-HPLC. Detection was performed by positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode, monitoring the transitions m/z 372.1-->m/z 312.2 and m/z 408.8-->m/z 237.9, for quantification of isradipine and IS, respectively. The standard calibration curves showed good linearity within the range of 10 to 5000 pg/mL (r(2)>or=0.9998). The lower limit of quantitation (LLOQ) was 10 pg/mL. The retention times of isradipine (0.81 min) and IS (0.65 min) suggested the potential for high throughput of the proposed method. In addition, no significant metabolic compounds were found to interfere with the analysis. This method offered good precision and accuracy and was successfully applied for the pharmacokinetic and bioequivalence studies of 5 mg of sustained-release isradipine in 24 healthy Korean volunteers.

Validated LC-MS/MS method for quantification of gabapentin in human plasma: application to pharmacokinetic and bioequivalence studies in Korean volunteers.

A sensitive validated liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for gabapentin (GB) in human plasma has been developed and applied to pharmacokinetic (PK) and bioequivalence (BE) studies in human. In a randomized crossover design with a 1-week period, each subject received a 300 mg GB capsule. The procedure involves a simple protein precipitation with acetonitrile and separated by LC with a Gemini C(18) column using acetonitrile-10 mm ammonium acetate (20:80, v/v, pH 3.2) as mobile phase. The GB and internal standard [(S)-(+)-alpha-aminocyclohexanepropionic acid hydrate] were analyzed using an LC-API 2000 MS/MS in multiple reaction monitoring mode. The ionization was optimized using ESI(+) and selectivity was achieved using MS/MS analysis, m/z 172.0 --> 154.0 and m/z 172.0 --> 126.0 for GB and IS, respectively. The assay exhibited good linearity over a working range of 20-5000 ng/mL for GB in human plasma with a lower limit of quantitation of 20 ng/mL. No endogenous compounds were found to interfere with the analysis. The accuracy and precision were shown for concentrations over the standard ranges. This method was successfully applied for the PK and BE studies by analysis of blood samples taken up to 36 h after an oral dose of 300 mg of GB in 24 healthy volunteers.

Effect of Korean oriental medicine extract on bone mass as compared with alendronate in ovariectomized rats.

A number of alternative medicines (AMs) have often been used as traditional therapies for various diseases without scientific or clinical evidence supporting their use. The present study examined the pharmaceutical effects of an AM extract with a long history of use as a traditional medicine for various bone diseases. To evaluate it as a potential candidate for use as an anti-osteoporotic drug, we investigated the effects of the AM extract on the progression of bone loss in ovariectomized (OVX) rats fed a calcium (Ca)-deficient diet for 4 or 12 weeks. We also compared the AM extract with alendronate, an anti-resorptive drug. The AM extract did not influence bone turnover as indicated by biochemical markers [i.e., deoxypyridinoline (DPD)]. In contrast, alendronate treatment seemed to reduce bone turnover via inhibition of bone resorption as evidenced by reduced urinary DPD concentrations accompanied by a tendency for decreased serum tartrate-resistant acid phosphatase. Administration of alendronate or AM extracts did not significantly affect bone density, although both tended to increase bone mineral density (BMD) and bone strength of the femur. Although both treatments did not affect vertebral BMD and bone strength, histological analysis of vertebrae showed well-developed trabecular networking in OVX rats treated with alendronate or AM extract, in contrast to the thin and disconnected trabecule in OVX rats. In conclusion, the AM extract produced a very weak effect on the prevention of bone loss induced by OVX and Ca deficiency in rats, but was similar to the results observed with alendronate. Further verification is necessary to justify the use of the AM extract as a treatment for osteoporosis.