Elevation of serum creatine kinase induced by anti-thyroid drugs: Two case reports and a literature review.

Anti-thyroid drugs (ATDs), such as methimazole (MMI) and propylthiouracil (PTU), are the most common treatment options for hyperthyroidism. Although effective, well-known adverse effects include agranulocytosis, toxic hepatitis, vasculitis, and arthralgias. Myalgia and elevation of serum creatine kinase (CK) are relatively rare, with an unclear mechanism. Rapid decrease in the thyroid hormone level may be associated with ATD-related myopathy; however, direct effects of the drug on muscle tissue cannot be excluded. Here we report on two Chinese patients with myalgia and an elevated CK due to ATDs. Early recognition of this rare medication-induced adverse effect and close monitoring of the CK level are particularly important. Physicians and pharmacists should inform the patients about the earliest symptoms of adverse effects for patients to know when to discontinue the drug. If adverse events occur, different treatment strategies such as ATD dose reduction and switching to alternative ATDs can be applied depending on the case.

Determination of talinolol in human plasma by high performance liquid chromatography-electrospray ionization mass spectrometry: application to pharmacokinetic study.

A rapid and sensitive method for determination and screening in human plasma of talinolol is described using propranolol as the internal standard. The analytes in plasma were extracted by liquid-liquid extraction using methyl t-butyl ether. After removed and dried the upper organic phase, the extracts were reconstituted with a fixed volume of buffer of ammonium acetate and acetonitrile (60:40, v/v). The extracts were analyzed by a HPLC coupled to electrospray ionization mass spectrometry (HPLC-MS/ESI). The HPLC separation of the analytes was performed on a Phenomenex C18 (250 mmx4.6 mm, 5 microm, USA) column, with a flow rate of 0.85 mL/min. The complete elution was obtained within 5.5 min. The calibration curve was linear in the 1.0-400.0 ng/mL range for talinolol, with a coefficient of determination of 0.9996. The average extraction recovery was above 83%. The methodology recovery was between 101% and 102%. The limit of detection (LOD) was 0.3 ng/mL for talinolol. The intraday and inter-day coefficients of variation were less than 6%. This HPLC-MS/ESI procedure was used to assess the pharmacokinetics of talinolol. A single oral 50 mg dose of talinolol tablet was administered to 12 healthy Chinese volunteers, the main pharmacokinetic data are as follows: Cmax was 147.8+/-63.8 ng/mL; tmax was 2.0+/-0.7 h; t1/2 was 12.0+/-2.6 h. The method is accurate, sensitive and simple for the pharmacokinetic study of talinolol.

Determination of ambroxol in human plasma by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI).

A rapid, sensitive and specific method to determination of ambroxol in human plasma using high performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-MS/ESI) was described. Ambroxol and the internal standard (I.S.), fentanyl, were extracted from plasma by N-hexane-diethyl ether (1:1, v/v) after alkalinized with ammonia water. A centrifuged upper layer was then evaporated and reconstituted with 100 microl mobile phase. Chromatographic separation was performed on a BDS HYPERSIL C18 column (250 mmx4.6 mm, 5.0 microm, Thermo electron corporation, USA) with the mobile phase consisting of 30 mM ammonium acetate (0.4% formic acid)-acetonitrile (64:36, v/v) at a flow-rate of 1.2 mL min(-1). The total run time was 5.8 min for each sample. Detection and quantitation was performed by the mass spectrometer using selected ion monitoring at m/z 261.9, 263.8 and 265.9 for ambroxol and m/z 337.3 for fentanyl. The calibration curve was linear within the concentration range of 1.0-100.0 ng mL(-1) (r=0.9996). The limit of quantification was 1.0 ng mL(-1). The extraction recovery was above 83.3%. The methodology recovery was higher than 93.8%. The intra- and inter-day precisions were less than 6.0%. The method is accurate, sensitive and simple for the study of the pharmacokinetics and metabolism of ambroxol.