[Simultaneous determination of salidroside and tyrosol in Beagle dog plasma using UHPLC-MS/MS after pre-column dansyl chloride derivatization].

A pre-column derivatization method combined with UHPLC-MS/MS was developed for the simultaneous determination of salidroside and tyrosol in Beagle dog plasma. After protein precipitation by acetonitrile, the liquid supernatant was treated with dansyl chloride under dark conditions at 60 ℃ for 30 min, and then, the sample solution was extracted using methyl tertiary butyl ether. The multiple reaction monitoring in positive ion mode was used for MS detection of the tested analytes with the specific ion transitions of m/z 534.2→372.0 for salidroside derivative, m/z 372.0→171.0 for tyrosol derivative and m/z 506.0→171.0 for arbutin derivative. The chromatograph separation was achieved on an ACQUITY UPLC® BEH C18 column (100 mm × 2.1 mm, 1.7 µm) with a gradient mobile phase consisting of acetonitrile (0.1% formic acid)-water (10% acetonitrile, 0.1% formic acid) for 9 min. The assay showed a good linearity over the range of 0.02/0.1 − 20/10 µmol·L−1 with a lower limit of quantitation of 0.02 and 0.1 µmol·L−1 for salidroside and tyrosol in dog plasma, respectively. The intra- and inter-day precisions were all less than 8.68%, and the accuracy was within ±11.4%. The established method with a high sensitivity, good specificity and reliability was appropriate for simultaneous determination of salidroside and tyrosol in dog plasma and successfully applied to a pharmacokinetic study after intragastric administration of salidroside to Beagle dogs.

[Simultaneous determination of clevidipine butyrate and its metabolite clevidipine acid in dog blood by liquid chromatography-tandem mass spectrometry].

A rapid, sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of clevidipine butyrate and its primary metabolite clevidipine acid in dog blood. After one-step protein precipitation with methanol, the chromatographic separation was carried out on an Ecosil C18 column (150 mm x 4.6 mm, 5 µm) with a gradient mobile phase consisting of methanol and 5 mmol · L(-1) ammonium formate. A chromatographic total run time of 13.0 min was achieved. The quantitation analysis was performed using multiple reaction monitoring (MRM) at the specific ion transitions of m/z 454.1 [M-H]- --> m/z 234.1 for clevidipine butyrate, m/z 354.0 [M-H]- --> m/z 208.0 for clevidipine acid and m/z 256.1 [M-H]- --> m/z 227.1 for elofesalamide (internal standard, IS) in the negative ion mode with electrospray ionization (ESI) source. The linear calibration curves for clevidipine butyrate and clevidipine acid were obtained in the concentration ranges of 0.5-100 ng · mL and 1-200 ng · mL(-1), separately. The lower limit of quantification of clevidipine butyrate and clevidipine acid were 0.5 ng · mL(-1) and 1 ng · mL(-1). The intra and inter-assay precisions were all below 12.9%, the accuracies were all in standard ranges. Stability testing indicated that clevidipine butyrate and clevidipine acid in dog blood with the addition of denaturant methanol was stable under various processing and/or handling conditions. The validated method has been successfully applied to a pharmacokinetic study of clevidipine butyrate injection to 8 healthy Beagle dogs following intravenous infusion at a flow rate of 5 mg · h(-1) for 0.5 h.

[Effects of Shenmai Injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure].

OBJECTIVE: To explore the effects of Shenmai Injection (SMI), a compound traditional Chinese herbal medicine, on pharmacokinetics and serum concentration of digoxin when applied together with digoxin. METHODS: Twenty dogs with heart failure were randomly divided into 4 groups: control group and low-, medium- and high-dose SMI groups, with 5 dogs in each group. After intravenous injection of digoxin injection at a dose of 7.41 µg/kg, dogs in the control group were administered intravenously with normal saline 20 mL daily for 5 d, and the other groups were intravenously administered with SMI at the doses of 0.517, 1.034 and 1.551 mL/kg respectively. After the administration, the blood was collected at designed time points. Serum concentration of digoxin was determined by high-performance liquid chromatography with electrospray tandem mass spectrometry (HPLC/MS/MS). RESULTS: The low-, medium- and high-dose SMI showed different effects on the pharmacokinetics of digoxin: the low-, medium- and high-dose SMI revealed a tendency to decrease the elimination half-life (T(1/2ß)) of digoxin. The low-dose SMI showed a tendency to decrease the digoxin concentration. Serum clearance (CL) in the low-dose SMI group was higher than that in the control, and also significantly higher than those in the medium- and high-dose SMI groups (P<0.05). The area under concentration-time curve (AUC(0→∞)) in the low-dose SMI group was lower than that in the control group (P=0.05); the AUC(0→72 h) and AUC(0→∞) in the low-dose SMI group were significantly lower than those in the medium- and high-dose SMI groups. Low-dose SMI accelerated the clearance of digoxin in blood. CONCLUSION: Low-, medium- and high-dose SMI shows different effects on pharmacokinetics of digoxin and reveals a tendency to shorten T(1/2ß) of digoxin. Low-dose SMI can accelerate the clearance of digoxin in blood.

[Tissue distribution and excretion of bromotetrandrine in rats].

AIM: To study the tissue distribution and excretion of bromotetrandrine (W198) in rats. METHODS: The concentrations of W198 in biological samples were determined by an HPLC method with UV detection. RESULTS: After a single i.v. dose of 20 mg x kg(-1) W198 in rats, the parent drug concentrations in tissues were higher than those in blood at the same time. Parent drug was mainly distributed in lung, kidney, heart and liver, the peak levels were attained at 0.25 h and decreasing at 2 h after dosing in most tissues. After a single iv dose of 20 mg x kg(-1) W198 in rats, the excretion of the parent drug in urine, feces and bile amounted to 0. 150%, 2.1% and 0.063% of the dose, respectively. CONCLUSION: W198 was mostly distributed in lung. The parent drug excretion was less than 3% via urine, feces and bile.

[Pharmacokinetics of bromotetrandrin (W198) in rats and beagle dogs].

AIM: To study the pharmacokinetics of bromotetrandrine (W198) in rats and beagle dogs. METHODS: The concentrations of W198 in serum were determined using HPLC method with UV detection. RESULTS: The pharmacokinetic parameters of W198 after single iv doses of W198 10, 20 and 40 mg x kg(-1) in rats were as follows: T1/2beta were 6.60, 7.36 and 6.77 h, AUC0-24 h were 3.797, 7.371 and 15.192 mg x h x L(-1), Vd were 7.14, 4.33 and 4.13 L x kg(-1), CL were 2.83, 2.60 and 2.71 L x (kg x h)(-1), respectively. The T1/2beta and AUCo-24 h of W198 after single im dose of W198 20 mg x kg(-1) in rats were 11.61 h and 12.646 mg x h x L(-1). The im bioavailability of W198 in rats was 56.9%. The T1/2beta, AUC0-24 h, Vd and CL of W198 after single iv dose of W198 5 mg x kg(-1) in beagle dogs were 11.72 h, 12.646 mg x h x L(-1), 0.70 L x kg(-1) and 0.46 L x (kg x h)(-1), respectively. The plasma protein binding ratio of W198 with human serum protein was 78.0%. CONCLUSION: The absorption of W198 in rats was of first order kinetics.