Clarithromycin standard

The next step is to determine the practical detection limit (pDL) based on the signal-to-noise ratio at the lowest level at which the analyst can get the HPLC system to function reproducibly on injections of a standard at a known concentration (S/N ratio of 3 1 is a rule of thumb). Then the practical quantitation limit (pQL) is determined usually at a level 2-5 times the pDL and the repeatability of the standard at this level is determined. This pQL usually results in analyte concentrations of nanograms or micrograms per milliliter. The repeatability of a 1.0 pg/mL clarithromycin standard preparation is shown in Table 2. ... 

TABLE 2 Repeatability of 1-0 Mg/mL Clarithromycin Standard Preparation Injections... 

FIGURE 3 Chromatogram of a swab solution blank, I.O- jg/mL clarithromycin standard solution, and an authentic sample solution (a) swab blank, (b) 1.0 pg/mL standard, and (c) authentic sample. 

Liquid chromatography was performed on symmetry 5 p.m (100 X 4.6 mm i.d) column at 40°C. The mobile phase consisted of acetronitrile 0.043 M H PO (36 63, v/v) adjusted to pH 6.7 with 5 M NaOH and pumped at a flow rate of 1.2 ml/min. Detection of clarithromycin and azithromycin as an internal standard (I.S) was monitored on an electrochemical detector operated at a potential of 0.85 Volt. Each analysis required no longer than 14 min. Quantitation over the range of 0.05 - 5.0 p.g/ml was made by correlating peak area ratio of the dmg to that of the I.S versus concentration. A linear relationship was verified as indicated by a correlation coefficient, r, better than 0.999. 

The swabs present several problems. With swabs there are many steps that need to be validated to insure an accnrate result. The analyst must be able to quantitatively remove the analyte from the swab. The analyte is added to the swab as a solution, dried, and quantitatively extracted off for analysis. The preferable extraction solntion is the swabbing solvent. The HPLC mobile phase or a mobile phase component could be used, but would necessitate a dilution of the swabbing solution. Standard addition and recovery data of clarithromycin added to different lots of polyester fiber are present in Table 3. ... 

TABLE 3 Standard Addition and Recovery Data of Clarithromycin from Polyester Fiber... 

The treatment of HP has become increasingly difficult due to the frequency of antibiotic resistance and recurrence after successful treatment. In Peru, the recurrence rate of the infection is as high as 73% even after successful eradication. In this instance, recurrence is not attributed to antibiotic resistance but to re-infection of patients. In the United States, resistant HP is also of concern. The Helicobacter pylori Antimicrobial Resistance Monitoring Program (HARP) is a multicenter US network that tracks HP patterns of resistance. In 2004, HARP reported that 34% of 347 HP isolates tested were resistant to one or more antibiotics commonly used to treat HP infections.In the US, most antibiotic resistance is associated with metronidazole and clarithromycin, both standard treatment options for HP. Thus, antibiotic resistance and high re-infection rates strongly argue for the development of new therapeutic modalities to prevent and treat HP infections worldwide. 

A triple therapy regimen with combinations of clarithromycin or azithromycin plus ethambutol plus rifabutin is the current standard of care. However rifabutin may be omitted in HIV-infected patients on protease inhibitors because of significant interactions (Table 19). 

A very comprehensive multicenter, randomized, double-blind study of two parallel treatment arms (the MOSAIC study MOxifloxacin compared to Standard therapy in Acute Infectious exacerbations of Chronic infections) demonstrated the powerful clinical activity of moxifloxacin for the treatment of AECB. Five-day treatment with moxifloxacin (400 mg, once daily for 5 days) was found to produce clinical cure rates that were superior to those achieved with 7-day treatment with a standard antibiotic (amoxicillin 500 mg three times daily for 7 days clarithromycin 500 mg twice daily for 7 days cefuroxime 250 mg twice daily for 7 days) [184]. 

Resistant organisms. Initial resistance occurs in about 4% of isolates in the UK, usually to isoniazid. Multiple-drug-resistant tuberculosis, i.e. resistant to rifampicin and isoniazid at least, should be treated with three or four drugs to which the organisms are sensitive and should extend for 12-24 months after cultures become negative. Treatment of such cases requires expert management. Atypical mycobacteria are often resistant to standard drugs their virulence is low but they can produce serious infection in immunocompromised patients which may respond, e.g. to clarithromycin or a quinolone, often in combination. 

Variable-temperature SSNMR was used by Tozuka et to investigate the observed polymorphism in clarithromycin. Polymorphic interconversions were identified using both powder X-ray diffraction (PXRD) and CPMAS NMR. The authors performed quantitation of two polymorphs (forms I and II) using carbonyl resonances that exhibited 1 ppm resolution. Relaxation and CP rate constants were not taken into account instead, relative peak areas were adjusted using a term derived from the preparation and analysis of a known set of standard mixtures. The correlation coefficient of measured peak intensity and weight content was found to be >0.99. 

In a randomized, donble-blind, mnlticenter comparison of a 5-day course of gemifloxacin 320 mg/day with a standard 7-day regimen of clarithromycin 500 mg bd in 712 patients with acute exacerbations of chronic bronchitis, the most frequently reported gemifloxacin-related adverse events were diarrhea (5.1%) and nausea (4.3%) (13). 

In a randomized, controlled trial in 120 patients supplementation with inactivated Lactobacillus acidophilus tds significantly improved the efficacy of a standard 7-day regimen with rabeprazole 20 mg bd, clarithromycin 250 mg tds, and amoxicillin 500 mg tds (12). There was no significant difference in adverse effects between the two groups. Those reported were abdominal pain, nausea, and diarrhea. 

In a randomized, placebo-controlled trial in 60 healthy, asymptomatic subjects who screened positive for H. pylori, supplementation with Lactobacillus GG twice daily for 14 days significantly reduced the adverse effects (diarrhea, nausea, taste disturbance) and improved the overall tolerability of a standard 7-day eradication regimen consisting of rabeprazole 20 mg bd, clarithromycin 500 mg bd, and tinidazole 500 mg bd (13). 

Unfortunately, MAC is resistant to the standard drugs used for tuberculosis, such as isoniazid and pyrazinamide. Multiple agents such as rifampin, rifabutin (ansamycin), clofazimine, imipenem, amikacin, ethambutol, ciprofloxacin, clarithromycin, and azithromycin have varying degrees of in vitro anti-MAC activity. Controversy formerly existed as to whether treatment for MAC is beneficial, but data indicate that an aggressive therapeutic approach decreases symptoms... 

Gupta, S., and Siepman, H. (1992). Comparative safety and efficacy of clarithromycin vs. standard agents in the treatment of mild to moderate bacterial skin or skin structure infections. Presented at First International Conference on the Macrolides, AzaUdes and Streptogramins (Santa Fe, NM). 

The polymyxin program did not proceed into the clinic but translatability was still addressed using samples from patients treated with a variety of standard of care antibiotics (piperacilhn/tazobactam, vancomycin, penicillin V, tobramycin, gentamicin, ampicillin, cefuroxime, clindomycin, clarithromycin, cefepime, daptomycin IV, bumetanide, vibramycin, and cyclophosphamide) compared to samples from healthy volunteers. This sample set was analyzed for sCr, BUN, urinary total protein, and urinary microalbumin as well as the emerging biomarkers urinary KIM-1, urinary NGAL, and urinary NAG. Much like the large animal studies with polymyxin B, the response for the antibiotic-treated cohort produced increases in all urinary- and serum-based... 

Taninaka et al measured erythromycin, roxithromycin and azithromycin in rat plasma using clarithromycin as the internal standard, or clarithromycin using roxithyromycin as the internal standard. Plasma (0.15 mL) was extracted with MTBE and HPLC used an ODS-modified silica column. In contrast to the method described by Kees et a single eluent (acetonitrile-aq. phosphate buffer,... 

The macrolide antibiotics clarithromycin (and its metabolite 14-hydroxyclari-thiomycin) and azithromycin (roxithromycin internal standard) were isolated from plasma and quantitated on a cyanopropyl column (electrochemical detection at +0.85 V). Azithromycin was eluted in 12 min with a 500/600/50 water (50 mM phosphate at pH 6.8)/acetonitrile/methanol mobile phase [1345]. The clarithiomy-cins were separated and eluted m 20 min with a 450/300/50 water (50 mM phosphate at pH 7.5)/acetonitrile/methanol mobile phase. The authors noted that phosphate buffers were chosen over ammonium buffers because the background noise was considerably higher with the latter. Linear ranges in the 0.025-5 pg/mL range and detection limits of 0.5-1.5 ng injected (S/N = 3) were reported (analyte dependent). 

The treatment paradigm that is most frequently used is triple therapy with PPIs in combination with amoxicillin and clarithromycin. Usually this is a twice-daily treatment with omeprazole/lansoprazole/pantoprazole at standard dose with 1 g amoxicillin and 500 mg clarithromycin taken simultaneously, which in trials have given 90% eradication. Metronidazole may be used in substitution for either antibiotic. 

Niemi, M. Neuvonen, P.J. Kivisto, K.T. The cytochrome P4503A4 inhibitor clarithromycin increases the plasma concentrations and effects of repaglinide, Clin.Pharmacol.Ther., 2001, 70, 58-65. [LC-MS LOQ 50 pg/mL indomethacin is internal standard]... 

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