Development and validation of LC-MS/MS methods to measure tobramycin and lincomycin in plasma, microdialysis fluid and urine: application to a pilot pharmacokinetic research study.

Background The aim of our work was to develop and validate a hydrophilic interaction liquid chromatography-electrospray ionization-tandem mass spectrometry (HILIC-ESI-MS/MS) methods for the quantification of tobramycin (TMC) and lincomycin (LMC)in plasma, microdialysis fluid and urine. Methods Protein precipitation was used to extract TMC and LMC from plasma, while microdialysis fluid and urine sample were diluted prior to instrumental analysis. Mobile phase A consisted of 2 mM ammonium acetate in 10% acetonitrile with 0.2% formic acid (v/v) and mobile phase B consisted of 2 mM ammonium acetate in 90% acetonitrile with 0.2% formic acid (v/v). Gradient separation (80%-10% of mobile phase B) for TMC was done using a SeQuant zic-HILIC analytical guard column. While separation of LMC was performed using gradient elution (100%-40% of mobile phase B) on a SeQuant zic-HILIC analytical column equipped with a SeQuant zic-HILIC guard column. Vancomycin (VCM) was used as an internal standard. A quadratic calibration was obtained over the concentration range for plasma of 0.1-20 mg/L for TMC and 0.05-20 mg/L for LMC, for microdialysis fluid of 0.1-20 mg/L for both TMC and LMC, and 1-100 mg/L for urine for both TMC and LMC. Results For TMS and LMC, validation testing for matrix effects, precision and accuracy, specificity and stability were all within acceptance criteria of ±15%. Conclusions The methods described here meet validation acceptance criteria and were suitable for application in a pilot pharmacokinetic research study performed in a sheep model.

Preparation, evaluation and application of core-shell molecularly imprinted particles as the sorbent in solid-phase extraction and analysis of lincomycin residue in pasteurized milk.

In this study, core-shell lincomycin-imprinted polymers were successfully synthesized and their binding properties evaluated. The functional monomers of methacrylamide and acrylamide were used for synthesis of core and shell, respectively. The optimum synthesized core-shell molecularly imprinted polymer (MIP) was applied as a sorbet in solid phase extraction cartridge. Afterwards, the method of core-shell molecularly imprinted solid phase extraction (CSMISPE) was used for pre-concentration and clean-up of lincomycin in the milk matrix prior to analysis via high performance liquid chromatography equipped with UV detector (HPLC-UV). The linear range for analysis of lincomycin in the milk matrix using introduced method was obtained from 0.08 to 2 µg/mL with recovery range of 80%-89%. The limit of detection and limit of quantification were 0.02 µg/mL and 0.08 µg/mL, respectively. Finally, calibrated CSMISPE-HPLC-UV method was used for lincomycin residue checking and quantification in the pasteurized milk samples of Mashhad city market.

Sensitive and specific determination of clindamycin in human serum and bone tissue applying liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry.

A method for the quantification of clindamycin in human serum and in human bone tissue samples applying high-performance liquid chromatography with atmospheric pressure chemical ionization-mass spectrometry (APCI-MS) is presented. Lincomycin is used as the internal standard. Serum samples are prepared only by protein precipitation with acetonitrile. Bone tissue samples have to be crushed and homogenized in extraction buffer prior to analysis. The chromatographic separation is achieved on an RP-18 stationary phase with 0.02% trifluoroacetic acid in water 60%/ acetonitrile 40% v/v as mobile phase. The limits of quantification are 0.1 microg/ml for serum samples and 0.1 microg/g for bone tissue samples. The coefficients of variation for the assays are 4.48 and 8.41% at the limit of quantification for serum and bone tissue samples, respectively. Bone tissue samples as small as 50 mg can be used.

[Substantiation of hygienic standard of lincomycin in the air of the work area]. / Obosnovanie gigienicheskogo standarta linkomitsina v vozdukhe rabochei zony.

The main parameters of lincomycin toxicometry were studied in animals. It was shown that the compound was low toxic after its oral or intraperitoneal administration in single doses, had no local irritant and skin resorptive effects and did not accumulate. The allergenic properties were slightly pronounced. The intoxication picture after a single inhalation was characterized by renal dysfunction, erythropenia, neutrophilia, lymphopenia and impairment of the normal intestinal microflora. The zone of the specific antimicrobial effect was equal to 8. On chronic inhalation, the signs of the specific antimicrobial effect were of the paramount importance: Limch am was equal to 4.7 mg/m3 and Limch exceeded 18.3 mg/m3. In the concentrations used, the substance had no embryotoxic and gonadotropic effects. The level of 0.5 mg/m3 (for Hazard Class 2) was recommended and approved as the maximum allowable concentration.

International standards and international reference preparations: amphotericin B, vancomycin, capreomycin, cefalotin, demethylchlortetracycline, gentamycin, gramicidin S, kanamycin and kanamycin B, lincomycin, lymecycline, methacycline, paromomycin, rifamycin SV, ristocetin and ristocetin B, spiramycin, and triacetyloleandomycin.

Each of the preparations described here was obtained and evaluated at the request of a WHO Expert Committee on Biological Standardization. Unless otherwise stated, a standard procedure was used to distribute the material into individual ampoules. The procedure was as follows. Upon receipt by the National Institute for Medical Research (NIMR), London, materials were stored temporarily in the dark at a temperature of -10 degrees C or lower, and protected from moisture. At a convenient time they were brought back to room temperature, mixed, and distributed into individual neutral glass ampoules so that each ampoule contained 50-100 mg of powder. If it was known that the material was light-sensitive non-actinic glass ampoules were used. After exhaustive drying in vacuum over phosphorus(V) oxide, the ampoules were either constricted (up to 1963) or fitted with capillary leak plugs, dried for a further period under the same conditions, filled with dry nitrogen, and sealed by fusion of the glass. The total drying period varied from 8 to 38 days according to the nature of the material. After they had been tested for leaks, the ampoules were stored in the dark at -20 degrees C.